Niacin & Weight Loss or Gain? How Vitamin B3 Affects Body Weight

Niacin (vitamin B3), also referred to as nicotinic acid, is a human nutrient that functions as a precursor to NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate).  NAD is a coenzyme recognized for its involvement in the catabolism of fats, carbohydrates, and proteins, as well as sending signals for DNA repair.  NADP is a coenzyme that modulates anabolic reactions such as synthesis of cholesterol and fatty acids.

Adequate niacin intake is necessary to prevent onset of a medical condition known as pellagra in which symptoms of diarrhea, dermatitis, and dementia occur.  In effort to eradicate pellagra (and diseases stemming from vitamin deficiencies), a food fortification program was implemented to enrich food products with vitamins (including niacin).  Fortified foods make it easy for adults living in developed countries to attain the recommended daily allowance (RDA) of niacin set between 16 mg and 18 mg.

Despite a recommended niacin intake of 16 mg to 18 mg per day for adults, some individuals administer mega-dose niacin supplements (between 500 mg and 2000 mg) for the treatment of hypercholesterolemia and/or hyperlipidemia.  Although mega-doses of niacin supplements are safe, effective, and tolerable for treating high cholesterol and lipids, they are not regarded as useful for other medical conditions.  Nonetheless, a circulating belief among many communities is that niacin supplements can help people lose weight.

Niacin & Weight Loss: Why People Think It Works…

It is unclear as to why people believe niacin supplements promote weight loss.  The drug Niaspan (extended-release niacin) has been on the market since 1997, yet there’s zero evidence to suggest that it causes weight change (gain or loss) at doses of 500 to 2000 mg per day.  The layperson likely believes niacin helps with weight loss because they’ve read that it’s involved in metabolism.  Other reasons as to why people believe niacin causes weight loss include: it’s flushing effect, it’s inclusion in certain weight loss formulas, and/or that they’ve personally lost weight while taking it.

• Catabolism of dietary fat: When some hear that niacin plays a role in the catabolism or breakdown of dietary fat, they assume that it’s somehow burning their body fat OR will prevent increases in body fat after eating. There’s no reason to think that niacin burns preexisting body fat or prevents fat gain resulting from excessive caloric intake.  If anything, most research suggests that excessive intake of niacin (such as from supplements) may prevent fat loss.  The only thing niacin does is support the conversion of fat to energy.
• Role in metabolism: It’s common for people to hear that niacin plays a role in metabolism and assume that by increasing niacin, that it’s somehow “speeding up” their basal metabolic rate (BMR). Speeding up basal metabolic rate (BMR) is associated with quicker burning of calories from food, burning more body fat stores, and rapid weight loss.  The truth is that while niacin is a precursor to coenzymes that support the metabolism of fats, proteins, and carbs – it doesn’t affect basal metabolic rate (BMR).  In other words, sufficient niacin helps your body form the coenzyme NAD to convert fats, proteins, and carbs to energy – but will NOT affect the amount of calories your body burns.  Extra niacin doesn’t somehow speed up the conversion of fats, proteins, or carbs to energy, and even if it did, your body would still store excess energy as body fat for later usage.  The energy that your body burns will be determined by your genetics, body composition/size, gut bacteria, sex, and physical activity.
• Flushing effect: Not only do some believe that niacin is burning fat stores within the body, but they take things one step further by assuming that the “flushing” they experience is associated with a purging of the burned fat. When taking mega-doses of niacin, it is common to experience a flushing reaction.  This flushing is a result of activation of G protein-coupled receptor 109A (GPR109A) which increases prostaglandins D2 and E2 plus arachidonic acid.  Subsequently, this activates the DP1, EP2, and EP4 prostaglandin receptors in capillaries to cause vasodilation and a flushing effect.  The flushing is NOT somehow caused by burning and/or elimination of fat stores throughout the body.
• Constituent in weight loss pills: A subset of fat burners, weight loss pills, and vitamins include and/or formerly-included niacin as a constituent. The fact that niacin was in some weight loss supplements lead many to believe that it played a critical role in any weight loss that users experienced.  While niacin may be included in weight loss formulas, there’s no evidence that it’s presence contributes to an alleged weight loss effect.  Furthermore, the amount of niacin present within weight loss formulas may be simply to ensure that the user is getting his/her RDA of niacin while on a restricted diet, rather than to induce actual weight loss.
• Lost weight while taking it: There are anecdotes online of persons who claim to have lost weight OR claim to know someone who lost weight while taking niacin. Even if you managed to lose weight while supplementing with niacin, it doesn’t necessarily mean that niacin facilitated the weight loss effect.  If you altered your diet, exercised more, consumed fewer calories, etc. – you probably would’ve lost weight regardless of the niacin supplementation.  While it is theoretically possible that specific does and/or types of niacin may promote weight loss in some individuals, the effect is unlikely.  Unless you can rule out all other confounding factors for your weight loss, it’s probably not accurate to assume that it was caused by niacin.
• Cholesterol and lipids: It is medically documented that niacin administration (500 mg to 2000 mg per day) can normalize concentrations of cholesterol (HDL, LDL, total cholesterol) and triglycerides. The effect of cholesterol and lipid modulation is achieved through niacin’s ability to limit cholesterol and lipid synthesis within the liver.  Though many associate healthy concentrations of cholesterol and triglycerides with a healthy body weight, there’s no evidence to suggest that niacin-induced changes in cholesterol/lipids will somehow promote weight loss.

How Niacin May Cause Weight Loss (Possibilities)

There’s not much support for the idea that niacin supplementation promotes weight loss.  Assuming niacin supplementation is capable of causing weight loss, there are only a few ways by which it is likely to do so, including: carnitine modulation, its side effects, increased energy levels, and toxicity.  The most likely of the means by which niacin induces weight loss is its side effect profile including: diarrhea, nausea, vomiting, and appetite loss.  Should you lose weight from supplementing with niacin, below is an explanation of mechanisms that might explain the reduction in bodyweight.

Adiponectin increase: Another possible way by which niacin supplementation might induce weight loss and/or enhance preexisting weight loss efforts is by upregulating concentrations of adiponectin, a protein hormone implicated in glucose regulation and fatty acid oxidation.  Research by Ukkola and Santaniemi (2002) suggests that adiponectin concentrations are inversely correlated with body fat percentage in adults.  A report by Fasshauer, Paschke, and Stumvoll (2004) mentions that adiponectin induces insulin sensitivity, upregulates anti-inflammatory markers, and that adiponectin levels are abnormally low among individuals with obesity compared to non-obese persons.

Normative concentrations of adiponectin are theorized to protect against onset of obesity, as well as obesity-related medical conditions including: non-alcoholic fatty liver disease, obesity, type 2 diabetes, and atherosclerosis.  In a study by Reinehr, Roth, Menke, and Andler (2004) the hormones, bodyweight, and body fat were tracked over a 1-year duration among 42 obese children.  After the 1-year term, all children were divided into 2 groups based on degree of weight loss: those who lost significant weight (16 children) AND 26 those who failed to lose weight (26 children).

Results of the study indicated that adiponectin concentrations were markedly different between the 2 groups.  Specifically, adiponectin levels were substantially higher among the 16 children who lost a significant amount of weight compared to the 26 who didn’t.  Moreover, the increased adiponectin was associated with attenuation of insulin resistance and decreased body fat.

Although elevated adiponectin is a byproduct of weight loss, it’s also possible that increasing adiponectin may promote weight loss through numerous mechanisms including reversal of insulin resistance.  Research by Yamauchi, Kamon, and Waki (2001) suggests that adiponectin plus leptin act synergistically to reverse insulin resistance in animal models.  Insulin resistance is understood to cause weight gain due to inability of the body to efficiently utilize energy from calories consumed.

The inability to utilize energy makes individuals with insulin resistance prone to fatigue, constant bouts of hunger, food cravings, and increased body fat storage.  Knowing that higher adiponectin levels are associated with lower body fat, reduced body weight, and insulin sensitivity – we could suspect that increasing adiponectin may promote weight loss.  Evidence from a trial by Westphal, Borucki, and Taneva (2007) indicates that niacin supplementation significantly increases adiponectin plus leptin in men diagnosed with metabolic syndrome.

After 6 weeks of supplementing with 1500 mg niacin (ER) per day, adiponectin levels in the men increased by 56% and leptin concentrations increased by 26.8%.  Though metabolic syndrome failed to improve, the significant changes in adiponectin and leptin markers was encouraging and may have lead to weight loss and/or reversal of metabolic syndrome over a longer term.  More evidence from an investigation by Plaisance, Lukasova, and Offermanns (2009) supports the idea that niacin supplementation stimulates adiponectin release.

It appears as though niacin activates the GPR109A receptor, which thereafter bolsters adiponectin secretion.  Knowing that niacin supplementation increases adiponectin, a biomarker associated with lower body weight and reduced insulin resistance, it is possible that its increase makes it easier for some individuals to lose weight.  The enhanced ability to lose weight following increases in adiponectin could be related to improved insulin sensitivity.

• Source: https://www.ncbi.nlm.nih.gov/pubmed/12436346
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Carnitine modulation: A means by which niacin supplementation might facilitate weight loss is through modulation of carnitine synthesis and uptake.  A study by Couturier, Ringseis, Most, and Eder (2014) discovered that high doses of niacin stimulate expression of genes implicated in carnitine biosynthesis and uptake in obese rats.  Specifically, niacin supplementation activates PPARs (peroxisome proliferator-activated receptors) whereby gene expression is altered to enhance carnitine uptake (via OCTN2) and synthesis (via gamma-BBD and 4-N-TMABA-DH).

When obese rats received diets containing 780 mg/kg of niacin, it significantly increased carnitine concentrations in plasma, skeletal muscle, and liver – compared to obese rats receiving diets with 30 mg/kg niacin (the standard amount).  The supratherapeutic niacin intake upregulated OCTN2, BBD, and TMABA-DH gene activity, which in turn increased carnitine concentrations.  Considering that obese rats exhibit carnitine deficiencies and these deficiencies are implicated in perpetuation of obesity, increasing carnitine concentrations with niacin supplementation has therapeutic potential.

Additionally, based on the fact that the obese Zucker rats used in this study are an established model of human obesity, it’s possible that supratherapeutic doses of niacin (in the form of a supplement) may exert analogous effects on carnitine levels in humans as it did within rats.  Improving carnitine synthesis and uptake could improve general health of persons with obesity, as well as promote weight loss.  Although we cannot assume that obese humans react the same to niacin supplementation as the obese Zucker rats, it’s a possibility that they may share commonalities.

Impairments in carnitine systems and concentrations have been linked to decreased fatty acid oxidation, mitochondrial dysfunction, and insulin resistance.  Through niacin-induced genetically-mediated upregulation in carnitine, it may be possible to reverse abnormalities in mitochondrial function, insulin secretion, and fatty acid oxidation seen among persons with obesity – ultimately helping them lose weight.  A paper by Flanagan, Simmons, Vehige, et al. (2010) supports the idea that increasing carnitine levels among people with obesity is useful.

Animal model studies with obese, insulin-resistant rats show that carnitine supplementation enhances glucose tolerance and markedly increases total energy expenditure – potentially facilitating weight loss.  While more research is necessary to determine whether niacin might modulate carnitine levels in humans via gene activation to promote weight loss, it’s a mechanism that may explain anecdotal weight reduction among obese individuals supplementing with supratherapeutic doses of niacin.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/25012467
• Source: http://www.ncbi.nlm.nih.gov/pubmed/20398344

Cognitive function: It is possible that niacin supplementation may reverse cognitive dysfunction, ultimately enhancing self-control/impulse control, whereby it becomes easier for individuals who are overweight/obese to lose weight.  Research by Bischof and Park (2015) indicates that being overweight/obese in midlife is associated with cognitive decline, as well as altered integrity of gray and white matter within the brain.  Obesity in midlife is also associated with increased risk of Alzheimer’s disease and vascular dementia.

An earlier report by Sellbom and Gunstad (2012) suggests that obesity may induce cognitive dysfunction and modulate neural structure within the brain.  Some propose that chronic low-level inflammation associated with obesity might be to blame for cognitive decline.  In any regard, it is possible that administration of high-dose niacin in the form of a supplement may protect against obesity-related neural changes and/or reverse cognitive dysfunction.

A study by Rennie, Chen, Dhillon, et al. (2015) suggests that nicotinamide (a form of niacin) may enhance cognitive function and/or protect against cognitive decline.  The researchers concluded that nicotinamide supplements may be a low-cost, non-toxic intervention to preserve cognitive function and possibly reverse deficits.  Prior work by Morris, Evans, Bienias, et al. (2004) discovered that niacin intake was linked to protection against development of Alzheimer’s disease and cognitive decline in elderly individuals (ages 65+).

Knowing that niacin may attenuate cognitive dysfunction and/or decline, this may lead to superior impulse control whereby it becomes easier for some individuals to cut back on calories and/or resist food cravings to lose weight.  Though cognitive normalization from an impaired state via niacin supplementation may only play a small role in augmenting weight loss efforts, it may be extremely useful for certain individuals.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/26107577
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Energy increase: A subset of individuals claim that niacin supplements increase mental and physical energy levels.  Though increased “energy” hasn’t been reported in scientific studies investigating the effects of niacin, it is possible that some individuals feel more energized from their supplementation.  In the event that you feel energized from niacin supplementation, this increased energy might lead to greater engagement in physical activity/exercise throughout the day.

Feeling energetic may also make it easier for individuals attempting to lose weight to adhere to a daily exercise regimen.  Ongoing adherence to an exercise regimen (as a result of increased energy) may induce far greater weight loss over an extended duration than expected.  Moreover, if niacin increases a person’s mental energy or psychological function, it might be easier to resist the temptation to consume unhealthy foods.

Inflammation reduction: Another way in which niacin supplementation could help some individuals lose weight is by decreasing inflammation.  A study by Ganji, Kashyap, and Kamanna (2015) administered niacin to cultured hepatocytes from humans with non-alcoholic fatty liver disease and compared its effects to that of a control. It was noted that non-alcoholic fatty liver disease is associated with deleterious accumulation of hepatic fat, upregulation in reactive oxygen species (ROS), as well as inflammatory markers (e.g. interleukin-8).

The results of this study show that niacin (0.25 mmol/L and 0.5 mmol/L) inhibits fat accumulation in the cultured hepatocytes by up to 62%.  It was also reported that niacin significantly decreased reactive oxygen species and downregulated concentrations of interleukin-8 (indicative of inflammation).  Researchers believe that the reduced generation of reactive oxygen species likely contributed to the decreased inflammation.

It is important to note that this study was conducted in a cultured cell line, not actual humans, therefore it remains unclear as to whether similar effects would be observed if niacin supplements were ingested.  Furthermore, the results of this study were limited to testing the effects of niacin on inflammatory markers in a cell line, not throughout the entire body (as is commonly seen among those with obesity).  That said, it is possible that niacin might decrease chronic inflammation implicated among those with obesity, making it easier to lose weight.

A study by Wanders, Graff, White, and Judd (2013) assigned 2 groups of mice to consume different diets, namely: a high-fat diet OR standard chow.  After continuing the diets for 6 weeks, researchers administered either a vehicle or niacin treatment for 5 weeks.  Results suggested that, among mice consuming the high-fat diets, niacin substantially increased anti-inflammatory biomarkers adipokine and adiponectin through modulation of gene expression and macrophages.

The researchers concluded that niacin administration is able to mitigate adipose tissue inflammation by enhancing adiponectin and expression of anti-inflammatory cytokines, while simultaneously decreasing pro-inflammatory cytokines.  The degree to which anti-inflammatory benefits were attained was contingent upon the number of niacin receptors within the mice.  While this study doesn’t prove that niacin decreases tissue inflammation in humans, it is possible that niacin might have similar effects in a subset of persons.

Research by Gregor and Hotamisligil (2011) discusses the associations between inflammation and obesity, as well as insulin resistance and type 2 diabetes.  It appears as though obesity induces low-level chronic inflammation resulting from metabolic cells receiving excess nutrients and energy.  This inflammation is widespread and affects adipose, brain, liver, muscle, and pancreatic tissue.

What’s more, researchers proposed that anti-inflammatory therapies might prove useful in treating insulin resistance and glucose intolerance – each of which can make it challenging to lose weight.  A report by Sears and Ricordi (2011) notes that it may be possible to treat obesity (and comorbidities) by decreasing inflammation.  Assuming niacin exerts an anti-inflammatory effect throughout the body and reverses insulin resistance plus glucose intolerance, it might help with weight loss.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/26024755
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Mitochondrial function: Another possible means by which niacin supplementation might promote weight loss and/or combat obesity is by improving mitochondrial function.  A study by Jia, Li, Gao, et al. (2008) administered niacin to a model of 1-MPP (1-methyl-4-phenylpyridinium)-induced cellular model of Parkinson’s disease.  Mitochondrial function of the cells was measured by analyzing alpha-ketoglutarate dehydrogenase activity.

Researchers discovered that administering nicotinamide at approximately 100-fold the quantity present within the cellular culture protected the mitochondria as evidenced by normative alpha-ketoglutarate dehydrogenase activity following 1-MPP exposure.  Furthermore, the high-dose nicotinamide reduced generation of reactive oxygen species, DNA damage, and protein oxidation.  While we cannot assume that administration of high-dose niacin in the form of a dietary supplement yields the same protective effects in humans as it did in the cell line, the it’s a possibility.

A study by Khan, Auranen, Paetau, et al. (2014) shows that nicotinamide riboside (NR), a precursor to niacin and NAD(+), boosts NAD(+) concentrations in ice and promotes mitochondrial biogenesis (growth of new mitochondria).  In a model of mitochondrial myopathy, neuromuscular disease caused by damage to the mitochondria, nicotinamide riboside (NR) induced mitochondrial biogenesis in adipose tissue and skeletal muscle.  Though nicotinamide riboside is not the same as niacin, it is possible that niacin supplementation might also protect and/or reverse mitochondrial dysfunction seen in obesity.

Work by Crescenzo, Bianco, Mazzoli, et al. (2016) specifically links mitochondrial dysfunction in the liver to onset of obesity, type 2 diabetes, and non-alcoholic fatty liver disease.  It is implied that that normalizing hepatic mitochondrial function might prove effective for the treatment of obesity and related health conditions.  Other research by Bournat and Brown (2010) suggests that excessive food consumption (and nutrient intake) among those with obesity leads to mitochondrial dysfunction and ROS generation.

Without properly functioning mitochondria, ATP levels are suboptimal, energy expenditure changes, and reactive oxygen species accumulate.  This ultimately affects glucose metabolism and might lead to increased storage of fat.  Given the findings suggestive that high-dose niacin may protect and/or reverse mitochondrial dysfunction, and others suggesting that improving mitochondrial function might enhance weight loss efforts, it’s possible that niacin supplementation could enhance mitochondrial function whereby it becomes easier for an obese individual to lose weight.

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Side effect-induced: The most probable means by which niacin causes weight loss in a subset of users is through side effects.  Common side effects associated with niacin supplementation include: flushing of the face and/or skin (warmth, redness, tingling, itching), stomach pain, diarrhea, nausea, vomiting, and gastrointestinal distress.  Assuming you were to experience side effects such as stomach pain, diarrhea, nausea, or vomiting over an extended duration, it’s reasonable to assume that you might find it challenging to maintain an appetite or consume as much food as usual.

Most people experiencing stomach aches, diarrhea, nausea, and/or vomiting won’t feel hungry for food.  Even if you are hungry while taking niacin, you may cut back on your food intake in fear that excessive consumption may exacerbate niacin-related side effects.  In other words, you probably won’t eat large meals if you fear that they’re going to exacerbate an already-wicked stomach ache or induce vomiting.

In addition to decreased appetite (from side effects) and/or consciously decreasing caloric intake (in fear of aggravating preexisting side effects) certain side effects may directly cause weight loss.  For example, if you’re experiencing diarrhea you’ll end up losing weight from the laxative effect, however, this is not a healthy or sustainable way to keep weight off.  A subset of individuals have reported experiencing the rare side effect of “appetite loss” directly from niacin (as opposed to the appetite loss being caused by a niacin-induced side effect).

In the event that you are among the rare subset of individuals who experiences an appetite loss from supplementing with niacin, it may be easy to cut back on caloric intake to lose weight.  If this persists over an extended duration, weight loss may become more pronounced.  Still, since most people find that niacin side effects diminish over time and/or aren’t willing to put up with anorectic effects over a long-term, side effect-induced weight loss is considered uncommon.

Toxicity: Among the most plausible explanations regarding why some individuals lose weight from taking niacin supplements is that the large quantity of niacin ingested exerts a biologically toxic effect.  The recommended daily allowance (RDA) of niacin is under 20 mg for adults.  Those taking niacin in effort to lose weight are suspected to administer mega-doses ranging between 500 mg and 3000 mg – similar doses as those using niacin to treat hypercholesterolemia and hyperlipidemia.

For perspective, someone taking 2000 mg niacin per day is ingesting over 100-fold the RDA of niacin.  Some studies suggest that there’s a unique dose-response effect of vitamins on bodyweight in that, normative levels facilitate healthy body weights.  When levels moderately above the RDA are ingested, individuals tend to experience weight gain.  Extreme supratherapeutic doses (such as 100-fold the recommended daily amount) is toxic to the body.

Rather than exacerbating weight gain from moderately “above average” doses, the extreme mega-doses of vitamins induces toxicity whereby a slight weight loss effect is observed.  If you’re taking large doses of niacin and losing weight, there’s a chance that the weight reduction is related to toxicity.  Despite the fact that mega-dosing with niacin may induce a toxicity that causes weight loss, it’s unclear as to whether the toxicity is dangerous over the long-term based on the fact that mega-dosing with niacin to treat hypercholesterolemia seems safe and conducive to general health among those with the condition.

How Niacin Might Cause Weight Gain (Possibilities)

While there’s some evidence to suggest that niacin may modulate biological processes to enhance weight loss, there’s arguably stronger evidence to suggest that overconsumption of niacin may cause weight gain.  Sufficient quantities of niacin (18 mg per day for adults) are understood as beneficial for biological health, however, excessive intake of niacin (with supplementation) may cause weight gain by: inducing insulin resistance, increasing fat synthesis, disrupting neurotransmitter-related metabolism, and epigenetic modulation.  It is also possible that niacin could: decrease energy levels to cause fatigue, increase a person’s appetite, and/or alter levels of hormones to cause weight gain.

Appetite increase: A small percentage of niacin users report significant increases in appetite after high-dose supplementation.  If you happen to be in the unlucky subset of individuals who experiences a substantial appetite surge from niacin supplementation, you’re probably going to gain weight.  When appetite remains high over an extended duration, you’ll have a tougher time resisting food cravings and total caloric intake.

High appetite is difficult to control with willpower alone, and if the niacin supplementation is to blame, it’s only a matter of time before you succumb to the temptation of overeating.  Studies in animal models (cattle, chickens, rats) show that supratherapeutic niacin intake leads to increased daily feed intake.  This increased feed intake can likely be attributed to a niacin-induced upregulation in appetite and/or food cravings.

In all studies, increased feed intake from the niacin mega-doses resulted in body fat and weight gain.  If niacin causes your appetite to remain high over a long-term, you may overeat and gain weight similar to the animal models.  A vicious circle then forms in which niacin-induced high appetite promotes overeating, which in turn causes weight gain, and the additional weight gain reinforces likelihood of future overeating (accompanied by weight gain).

Fat synthesis & storage increase: Individuals who are overweight or obese generally accumulate excessive amounts of body fat.  It seems as though one means by which niacin could induce weight gain is via increasing fat synthesis and/or storage – especially when administered with other B vitamins.  A report by Zhou and Zhou (2014) mentions that Vitamin B1 and B6 synthesize fat from carbs and protein, but when other B vitamins are present, they appear to increase body fat in rats.

It is unclear as to whether niacin administration significantly amplifies fat synthesis in humans, leading to increased body fat.  That said, based on many animal studies suggesting that niacin supplementation increases body fat, one possible mechanism explaining this increase is amplification of fat synthesis.  If niacin is promoting an increase in fat synthesis, this may explain why some individuals taking niacin supplements experience weight gain – especially if they’re simultaneously supplementing with other B vitamins (e.g. in a vitamin B complex).

A study by Nelson, Vlazny, Smailovic, and Miles (2012) suggests that intravenously-administered niacin (2.8 mg/min) suppresses lipolysis in healthy and obese individuals, leading to more efficient storage of dietary fat.  Based on the results of this study, one might suspect that niacin supplementation induces an anti-lipolytic effect in adipose tissue, thereby interfering with efforts to reduce body fat and weight.  This is the opposite effect of a hypocaloric diet in which anti-lipolytic effects seen among those with obesity are reversed, ultimately leading to weight loss.

• Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932423/
• Source: http://www.ncbi.nlm.nih.gov/pubmed/22923472

Epigenetic changes: Those supplementing with niacin may also experience weight gain as a result of epigenetic changes.  There’s reason to believe that supratherapeutic doses of niacin might modulate gene expression, which in turn alters metabolism and leads to obesity.  Researchers Zhou and Zhou (2014) propose that excessive intake of niacin (and other vitamins) could contribute to epigenetic expression implicated in obesity.

They discussed that the biotransformation of niacin appears to increase demand for labile methyl groups, which could disturb DNA methylation through methyl group competition.  In one study, researchers tested the effect of nicotinamide on DNA methylation and discovered that high-dose administration over a long-term caused a substantial decrease in the methyl pool and concentrations of DNA methylation associated with altered gene expression.  Additionally, it was noted that nicotinamide supplements given to pregnant rats downregulated global DNA methylation in the brain and liver.

Though these findings were derived from rat studies and might not apply to humans, it is possible that similar epigenetic changes are induced by niacin supplementation in humans over a long-term.  Furthermore, it is possible that these epigenetic changes are just one mechanism by which weight gain may occur.

• Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932423/
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Enzyme upregulation: Taking niacin supplements may promote weight gain by increasing niacin-degrading enzymes.  A report by Zhou, Li, Chen, and Zhou (2015) highlights the fact that individuals with obesity exhibit lower serum levels of niacin compared to non-obese counterparts.  The lower serum levels of niacin are likely related to enzymatic overactivity stemming from long-term overconsumption of the vitamin.

In other words, when niacin intake exceeds biologically-necessary levels over an extended duration, enzymes implicated in metabolizing niacin are upregulated as an adaptation to handle the extra quantity, which inevitably is observed by researchers as reduced serum niacin concentrations.  Though it is possible that obesity itself causes an upregulation in niacin-degrading enzymes, it is also possible that an upregulation of niacin-degrading enzymes was a cause of weight gain.  In sum, niacin supplementation might upregulate certain enzymes to induce weight gain and/or interfere with weight loss.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/26322161

Fatigue: Administration of niacin could cause fatigue and/or reduce energy in a subset of users, possibly leading to weight gain.  If you experience fatigue or feel tired each time you supplement with niacin, this may make it difficult to maintain healthy physical activity levels throughout the day, ultimately lowering energy expenditure.  Though not confirmed in the literature, a subset of individuals have reported successful somnolence induction through administering 100 mg to 500 mg of niacin approximately 20 minutes before bedtime.

The mechanism by which niacin is capable of promoting fatigue and/or somnolence in certain individuals remains unknown.  That said, assuming niacin is interfering with your ability to stay alert and energized throughout the day, this might cause you to become sedentary and expend less energy.  The fatigue-related decrease in physical activity might explain why some individuals gain weight from niacin supplementation.

Glucose dysregulation: Another possible way niacin supplementation could cause weight gain is through induction of hyperglycemia or glucose dysregulation.  A report by Schwartz (1993) discusses a patient taking niacin for hypercholesterolemia who exhibited normalization of lipid markers as a result of treatment, but went on to develop a life-threatening case of hyperglycemia.  Research by Rindone and Achacoso (1996) investigated the effect of low-dose niacin on fasting glucose levels in 9 volunteers with non-insulin dependent diabetes.

All participants received niacin supplements at a dose of 1500 mg per day (divided into 3 doses of 500 mg) – over a 2-month duration.  Of the 6 completers, it appeared as though niacin therapy significantly increased fasting blood glucose concentrations from ~131 mg/dL to ~161 mg/dL.  Though this was a small-scale study, it shows that niacin supplementation (1500 mg/day) spiked fasting blood glucose, ultimately leading to hyperglycemia.

A review by Goldberg and Jacobson (2008) discovered that high-dose niacin supplementation (2.5 grams/day) increased fasting glucose by an average of 4% to 5%, which may not be significant, but could increase likelihood of weight gain.  Ding, Li, and Wen (2015) conducted a meta-analysis to determine the effect of niacin supplementation on glucose of patients with type 2 diabetes.  Results of the meta-analysis suggested that niacin supplementation significantly increased concentrations of fasting plasma glucose, leading researchers to recommend that niacin users regularly monitor their blood sugar levels.

Work by Chen, So, Li, et al. (2015) discovered that administration of niacin to obese mice lead to significant increases in blood glucose.  The mechanism by which blood sugar was increased involved GPR109A (G-protein coupled receptor 109A) activation within islet beta cells.  Based on research by Tomás, Lin, Dagher, et al. (2002) noting that hyperglycemia can induce insulin resistance when sustained over an extended duration, there’s reason to believe that niacin-induced hyperglycemia may lead to weight gain.

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• Source: http://www.ncbi.nlm.nih.gov/pubmed/12079834

Insulin resistance: Niacin might increase likelihood of weight gain by causing insulin resistance, a condition in which bodily tissues don’t respond properly to the secretion of insulin.  There are numerous studies supporting the idea that niacin supplementation, especially over the long-term, causes insulin resistance.  A study by Chang, Smith, Galecki, et al. (2006) assigned young and old individuals with normal glucose tolerance to receive nicotinic acid over a 2-week duration and discovered that niacin supplementation decreased insulin sensitivity in all age groups – with more pronounced reductions in the older individuals.

Heemskerk, van den Berg, Pronk, et al. (2014) investigated the effect of long-term niacin administration on insulin tolerance in mice over a 15-week duration.  After the 15-week trial period, an insulin tolerance test was administered and the mice exhibited insulin resistance throughout the entire body.  It appeared as though the insulin resistance was mediated through a downregulation of PDE3B (phosphodiesterase 3B) activity.

Blond, Rieusset, Alligier, et al. (2014) discovered that the pharmaceutical drug Niaspan (extended-release niacin) therapeutically decreases triglyceride concentrations, but unfavorably induces hepatic insulin resistance.  The occurrence of niacin-induced insulin resistance was evidenced by an inability of insulin to counteract endogenous glucose secretion.  A trial organized by Hu, Yang, Masuda, et al. (2015) also suggests that niacin supplementation causes insulin resistance.

In this trial, niacin (extended-release) at a dose of 1000 mg plus laropiprant (20 mg) were administered to 121 patients with dyslipidemia over a 4-week duration, then the doses were doubled and taken for an additional 8-week term.  Researchers measured lipids, glucose, insulin, and adiponectin concentrations at baseline and determined whether changes occurred throughout the trial.  Compared to pre-treatment baseline measures, glucose levels increased by ~13.1% and insulin levels increased by ~70.2%, indicating that niacin supplementation promotes insulin resistance.

While some propose that insulin resistance is protective against additional weight gain, others theorize that it may facilitate additional weight gain.  Insulin helps the body convert glucose to energy and store energy throughout your body for later usage.  When a person becomes resistant to insulin, the body is unable to fully utilize nutrients from within food.

This leads to fatigue and interferes with satiety, ultimately causing incessant hunger and food cravings.  As a result, individuals with insulin resistance may end up increasing their food consumption and gaining both body fat and weight.  Should you end up with niacin-induced insulin resistance, it’s not too farfetched to assume that the insulin resistance will be accompanied by weight gain.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/16757523/
• Source: http://www.ncbi.nlm.nih.gov/pubmed/2447344
• Source: http://www.ncbi.nlm.nih.gov/pubmed/24806747
• Source: http://www.ncbi.nlm.nih.gov/pubmed/26063948

Neurotransmitter modulation: Some research suggests that niacin may alter neurotransmitter systems to cause weight gain.  A substantial amount of evidence supports the idea that neurotransmitter systems regulate feeding behavior and energy expenditure in humans, including dopamine, norepinephrine, and serotonin.  To showcase this phenomenon, one can simply administer a dopaminergic reuptake inhibitor and releaser (e.g. amphetamine) and a person’s appetite will diminish plus he/she will have more physical energy to exercise.

If chronically administered, amphetamine can induce significant weight loss, however, the weight loss is unsustainable and not healthy.  It is understood that niacin plays a role in the conversion of folate to tetrahydrofolate, which in turn is converted to tetrahydrobiopterin.  Since tetrahydrobiopterin influences neurotransmitter synthesis, there’s reason to believe that niacin intake affects neurotransmitter concentrations throughout the brain.

It is reasonable to theorize that the effect of niacin supplementation on neurotransmitter synthesis may be most substantial among individuals with genetic polymorphisms associated with methylation and/or neurotransmitter degradation (e.g. COMT, MTHFR, etc.).  Regardless of genetic inheritance, when considering that neurotransmitter systems throughout the brain influence feeding habits, and that niacin supplementation could modulate these systems to increase feeding behavior (which has been observed in animal models given high-dose niacin), it’s reasonable to suspect that niacin-induced neurotransmitter modulation could be culpable for weight gain.  In addition, it appears as though niacin supplementation interferes with degradation of neurotransmitters via detoxification pathways.

For example, high levels of nicotinamide are shown to inhibit catecholamine degradation through depletion of sulfate and methyl groups.  Significantly inhibiting catecholamine degradation with niacin (and/or its metabolites) could markedly alter CNS activation.  Altered CNS activation could lead to lower energy (lethargy), increased appetite, food cravings, and ultimately weight gain.

• Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932423/

Reactive oxygen species: Despite the fact that niacin-induced elevations in reactive oxygen species (ROS) might cause weight loss and/or attenuate weight gain among those who supplement, there’s reason to believe that an upregulation in reactive oxygen species could facilitate insulin resistance and/or contribute to weight gain.  Research by Zhou, Li, Sun, et al. (2009) showed that nicotinamide overloading increases concentrations of the metabolite N(1)-methylnicotinamide in rats, which leads to decreases in NAD contents, NAD/NADH ratio, and increases H202 (indicative of oxidative stress).

Li, Sun, Zhou, et al. (2010) believe that niacin increases oxidative stress as evidenced by plasma levels of H202 after supplementation, and that the increased oxidative stress potentiates insulin resistance.  The mechanism by which excessive niacin might promote insulin resistance involves a combination of increased reactive oxygen species with a spike in blood glucose levels, each of which have been shown to occur after niacin supplementation.  The spike in blood glucose leads to insulin release all while the reactive oxygen species impair cellular function, ultimately interfering with insulin signaling.

The insulin signaling interference leaves blood glucose levels elevated and perpetuates insulin release.  Since the reactive oxygen species are eliminated at a faster rate than insulin, cell responses to the insulin recover swiftly, but after recovery, the uptake of glucose within tissues accelerates due to elevated insulin.  The net result is a plummeting of blood glucose, hunger, and increased feeding behavior.  For this reason, researchers believe that excessive consumption of niacin over a long-term could impair beta-cell function (possibly leading to failure), cause type 2 diabetes, as well as obesity – partially due to the generation of reactive oxygen species.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/19960564
• Source: http://www.ncbi.nlm.nih.gov/pubmed/20480523

Variables influencing niacin-related weight change…

There are many influential variables that determine whether a person is likely to lose weight, gain weight, or remain relatively weight neutral while taking niacin.  Influential variables that may influence the degree of weight change you experience from niacin supplementation include: dosage of niacin, regularity of administration, duration of supplementation, co-administered substances, and individual factors (e.g. administration details, genetics, medical conditions, etc.).  If you’re confused as to why you lost or gained weight while supplementing with niacin, you may want to assess and consider the interplay between these variables.

1. Niacin dosage (250 mg to 3000 mg)

The dosage of niacin administered on a daily basis may affect the degree of weight change a person experiences.  One hypothesis is that mild-to-moderate doses of niacin supplements (e.g. 250 mg to 1000 mg) are likely to cause weight gain, whereas mega-doses of niacin (e.g. 1000 mg to 3000 mg) are less likely to affect body weight and/or might even induce weight loss.  In other words, the dose-response effect of supplemental niacin on body weight may be such that a user is likely to gain weight up to a certain threshold, but when that threshold is exceeded, either: no change in weight is seen or slight weight loss occurs.

It is hypothesized that weight gain from low-to-moderate doses of niacin increase appetite and feeding behavior, resulting in a greater number of calories consumed.  Furthermore, it is suspected that low-to-moderate doses of niacin could interfere with glucose regulation and impair insulin sensitivity, each of which could play a role in weight gain.  Most individuals supplementing with mega-doses of niacin (1000 mg to 3000 mg) are ingesting between 50-fold and 150-fold the recommended daily allowance of niacin.

At these mega-doses, niacin is effective for controlling lipids by modulating cholesterol synthesis in the liver, however, extreme quantities of niacin may also induce a toxicity associated with substantial increases in oxidative stress.  The amplification of oxidative stress may inhibit weight gain and/or lead to weight loss in a subset of individuals.  That said, the hypothesized dose-response effect of niacin on body weight of humans hasn’t been thoroughly investigated in research over an extended duration.

Since the drug Niaspan (extended-release niacin) has been around since the late 1990s and isn’t associated with significant weight change in clinical trials, it is most logical to conclude that mega-doses of niacin (1000 mg to 3000 mg per day) don’t affect weight.  It is possible that each individual might experience slightly different dose-related effects of niacin on body weight based on factors such as dietary niacin intake, genetics, etc.  More research is necessary to determine whether low-to-moderate doses of niacin cause weight gain, as well as the approximate dose-related thresholds at which weight gain peaks and ceases.

2. Regularity of Administration

How regularly do you administer niacin supplements?  There’s some reason to believe that the regularity of your niacin administration may affect whether you experience significant weight change.  Research by Stielau and Meyer (1963) suggests that B-vitamin supplementation in successive doses is likely to induce weight gain in growing rats, whereas periodic B-vitamin supplementation is unlikely to spur weight change.

Though it is unclear as to whether similar outcomes might occur in humans supplementing with niacin, it is a possibility to consider.  For this reason, if you’re taking niacin on a daily basis, weight gain may be more likely to occur than if you were to take niacin on an infrequent, periodic basis.  Despite the hypothesis that more frequent administration is likely to cause weight gain, many individuals supplement with niacin on a daily basis to manage hypercholesterolemia or hyperlipidemia, yet weight change is seldom reported.

For this reason, it might be that regular niacin administration only increases body weight when low-to-moderate supplemental doses are administered (rather than the mega-doses used to treat high cholesterol).  In addition, the total duration over which a person has been using niacin might also dictate whether weight change occurs from regular administration.  For example, someone taking a moderate supplemental dose of niacin daily for 1 week may experience no change in weight, whereas if the daily dosing regimen is continued for 3 months, weight gain may ensue.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/14104386/

3. Duration of Supplementation

How long have you been supplementing with niacin?  The total duration over which you’ve been taking niacin might influence whether you gain weight, lose weight, or remain weight neutral.  Most individuals that have been taking niacin for an extremely short-term are unlikely to notice any weight change because they haven’t been using it long enough for biological changes to occur.  That said, if niacin alters your body weight, you’re likely to notice the effect over a moderate and/or long-term.

• Short-term: If you’ve been using niacin for a short duration (e.g. several days, a couple weeks, etc.), chances are that you won’t notice weight change. Assuming niacin is capable of increasing or decreasing your body weight, it is unlikely to occur rapidly, meaning it’ll be difficult to notice over a short-term (days or weeks of administration).  Additionally, over a short-term, you may still be titrating your dosage of niacin to an optimal amount for your particular medical condition and/or to minimize side effects.  Really the only way you’re likely to experience a noticeable weight change over a short-term is if you experience severe side effects (e.g. appetite loss, incessant diarrhea, nausea, vomiting) that interfere with your ability to consume and/or retain food.
• Moderate term: After a moderate term of niacin supplementation is when most weight changes will become noticeable to users. If you’ve been taking niacin for months, you’ve probably optimized your daily niacin dosage and know whether your weight is trending in a particular direction.  Animal studies suggest that low-to-moderate dose niacin supplementation stimulates appetite and induces noticeable weight gain over a moderate term compared to over a short-term.  It seems as though biological processes (e.g. glucose regulation, insulin secretion, etc.) are affected differently over a moderate-term from niacin supplementation than over a short-term.  For this reason, we might suspect that low-to-moderate supplemental dose (50 mg to 1000 mg) users might be more prone to weight gain than those using higher doses.  That said, if an individual is still experiencing side effects (e.g. appetite loss, diarrhea, nausea, vomiting) over a moderate term, he/she may have lost a considerable amount of weight.
• Long-term: If you’ve been taking niacin for a long-term (e.g. years), you probably know exactly how it affects your body weight. A long-term user will have titrated to an optimal dose of supplemental niacin for his/her condition, and the user’s biology will have adapted to regular administration of supratherapeutic doses.  Furthermore, side effects that influence weight through appetite modulation and/or food retention are likely to have diminished – otherwise the user would’ve discontinued niacin.  Research in animal models would lead to the hypothesis that low-to-moderate doses (e.g. 50 mg to 1000 mg) administered over a long-term would increase appetite and cause weight gain as a result of niacin-induced biological alterations (e.g. glucose levels, insulin secretion, etc.).  That said, high doses over a long-term (such as those used to treat hypercholesterolemia) don’t appear to cause weight gain in most users, likely due to the biological responses to the mega-dose.  Should niacin have induced weight change over a long-term, it’s likely to hit a plateau rather than continue indefinitely.

It is important to emphasize the fact that the dosage taken, as well as regularity of administration influence whether weight change occurs over a short or long-term of niacin supplementation.  Those taking lower doses (50 mg to 1000 mg) might be more prone to weight gain over an extended term than persons using high doses (1000 mg and up).  Moreover, if an individual uses his/her niacin supplements sporadically (e.g. once or twice per week), it’s unlikely to have any impact on the user’s weight.

4. Co-administered substances

When determining the effect niacin is likely to have on your body weight, you may want to consider the full daily “stack” or regimen of substances that you administer.  Co-administered substances (including pharmaceutical drugs, illicit substances, and other dietary supplements) might synergistically enhance certain effects of niacin on biological processes to promote weight change in a specific direction.  Other substances may offset niacin-related weight change OR might be more to blame for weight change than the actual niacin.

• Potentiators: Some substances might potentiate the weight change effects induced by niacin. The degree of potentiation in one direction or another may be contingent upon the specific dose of niacin administered, as well as the other drug that you’re taking.  For example, moderate doses of niacin (50 mg to 1000 mg) may alter blood glucose concentrations, ultimately leading to weight gain, and this effect may be amplified with a co-administered antipsychotic (also affecting glucose regulation) to promote a weight increase.  On the other hand, it has been proposed that large doses of niacin (1000 mg to 3000 mg) could cause weight loss in some users as a result of increased oxidative stress.  If a medication is administered that amplifies oxidative stress induced by niacin, this might enhance weight loss.
• Attenuators: Other substances may attenuate or negate any weight change that may have occurred as a result of niacin supplementation. For example, someone may end up using a drug or supplement that counteracts the biological changes induced by niacin that would’ve lead to weight gain.  Assuming niacin were to cause weight gain in a user by modulating blood sugar and/or insulin secretion, using diabetes medications or probiotics to regulate blood sugar may negate the niacin-induced mechanisms of weight gain.  Oppositely, assuming niacin were to cause weight loss by upregulating oxidative stress, taking a potent antioxidant to scavenge reactive oxygen species might negate the weight loss.  Keep in mind that attenuators of niacin-related weight change do not necessarily need to target the biological targets by which niacin induces weight change.  If niacin were to cause weight gain by spiking blood sugar, administration of a psychostimulant medication may not offset the blood sugar spike, but could reduce appetite, ultimately offsetting the niacin-related weight gain.
• Neutral substances (no effect): Before you automatically assume that a co-administered substance you’re taking is potentiating and/or attenuating the effect of niacin on your body weight, it is necessary to consider that other substances might have no effect. In other words, the co-administered substance that you’re using might be weight neutral and neither synergize nor antagonize the effect of niacin on your body weight.  Avoid falling into the trap of assuming that co-administered substances are always having an effect.

A final possibility to consider is that you mistakenly attributed any weight change you’re currently experiencing (weight loss or gain) to the niacin, when in reality the weight change is caused by a co-administered substance.  For example, niacin itself may be weight neutral in your biology, yet you wrongfully perceive the weight change you’re experiencing as having resulted from niacin – rather than the other drug you’re taking.  If you’re gaining weight while taking niacin and prednisone, the weight gain might be fully attributable to the prednisone.

One might also want to consider that co-administered substances could affect the pharmacokinetics of niacin, and that altered pharmacokinetics may influence degree of weight change resulting from supplementation.  High doses of niacin are thought to undergo hepatic metabolism through CYP450 enzymes including CYP2D6 and CYP3A4.  Anyone using a substance that induces and/or inhibits activity of the aforestated enzymes might experience weight changes stemming from pharmacokinetic alterations of niacin.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/15081432

Note: Some drugs have been theorized to deplete niacin reserves.  Depletion of niacin reserves from taking a certain pharmaceutical may mean that the dosage of your niacin supplement matters slightly more in regards to whether you’ll gain or lose weight.  If a drug is depleting 20 mg of niacin daily, and you’re supplementing with 1000 mg niacin per day, this may modify your biological dose-response to niacin and ultimately affect weight change.  Also, consider that the effects of niacin and any co-administered substances on your weight may be contingent upon dosing of each.

5. Individual factors

Multiple individuals may administer standalone niacin supplements at equal doses (e.g. 1000 mg), on a daily basis, for the same duration (e.g. 3 months) – yet one individual could experience weight gain, while the other experiences weight loss.  Given the similarities in niacin dosing, regularity of administration, and the duration of supplementation – it’s reasonable to suspect that weight changes should’ve been similar.  That said, individual factors such as: your age, administration details, body composition, dietary intake, genetics, medical diagnoses, and physical activity – might dictate how a person reacts to niacin supplementation in regards to weight change.

• Administration details: It is possible that the details associated with your niacin administration might influence whether you experience weight change, as well as whether the change is a gain or loss of body weight. Details of administration to consider include: whether niacin is taken on an empty, full, or partially-empty/full stomach, whether administered in a single or divided dose, and/or the time of day at which niacin is administered.  It is reasonable to expect that if niacin is taken on an empty stomach, it may cause more severe side effects that might influence weight (e.g. nausea) compared to if taken on a full stomach.  Additionally, taking niacin in a single (non-extended-release) pill is likely to affect biological processes differently than if taken in smaller doses at even time intervals throughout the day (e.g. 500 mg once every 4 hours).  Moreover, it is possible that taking niacin at night could yield entirely different biological effects (based on a user’s circadian rhythm) compared to administering it first thing in the morning or in the afternoon.  While these administration details may not make a huge difference in regards to weight gain, they could have a slight effect and therefore necessitate a brief mention.
• Body size / composition: Body size (height and weight) as well as composition (muscle and fat) might influence how long niacin stays in your system, which in turn could dictate whether you experience weight change during supplementation. Since niacin is hydrophilic (water soluble), it is thought that individuals with higher body fat and lower muscle will eliminate niacin from systemic circulation faster than others due to exhibiting fewer water stores.  Those with lower body fat and more muscle should retain niacin for a longer duration.  Not only could the duration niacin stays in your system influence degree of weight change you experience from supplementation, but your body size in respect to the dose your using might also be something to consider.  A person who’s 4’5” and weighs 95 lbs. may experience a more profound effect from 500 mg of niacin than an individual who’s 6’6” and weighs 250 lbs.  In summary, consider that the dose-response effect of niacin on body weight may be altered by body size and composition.
• Dietary intake: The macronutrient (proteins, fats, carbs) and micronutrient (vitamins, minerals, etc.) of your diet may affect whether you experience weight gain from niacin. Research suggests that excessive consumption of fortified foods (e.g. cereals) over a long-term may lead to weight gain on its own.  If you’re taking niacin supplements plus consuming nothing but fortified foods, you may be more likely to gain weight.  Understand that the amount of niacin you consume through your diet may affect the dose-response effect of supplementation on your weight.  Moreover, the quantities of other macronutrients and micronutrients you attain (e.g. excessive, normative, or insufficient) amounts could influence whether you gain or lose weight from niacin.
• Genetics: A person’s genes may play the biggest role in determining the dose-response effects of niacin on body weight. Anyone with polymorphic expression of the MTHFR and/or COMT genes might exhibit significantly different reactions to niacin compared to those with normative MTHFR and COMT expression.  That said, the dose-response effects of niacin on biology (and body weight) are not restricted to just the MTHFR and COMT genes – this would be far too simplistic of an explanation.  We know that high-dose niacin might necessitate hepatic isoenzymes (CYP2D6 and/or CYP3A4) for metabolism, and that certain polymorphisms of the CYP2D6 or CYP3A4 genes could influence dose-response effects of niacin on body weight.  Moreover, genes unrelated to metabolism (and epigenetic signatures) might influence how biology reacts to niacin and determine whether individuals lose weight, gain weight, or experience no weight change from supplementation.
• Medical conditions: Individuals with certain medical conditions may respond differently to niacin supplementation than those in normative health. The specific medical condition(s) that you’ve been diagnosed with might dictate whether niacin induces weight gain, weight loss, or has no effect on your body weight.  For example, it might turn out that niacin is more likely to cause weight gain among persons with type 2 diabetes (as a result of glucose dysregulation) than others.  On the other hand, it’s possible that niacin promotes weight loss among persons with an entirely different medical condition.  Some medical conditions like hepatic impairment, renal dysfunction, and small-intestinal bacterial overgrowth (SIBO) could affect the pharmacokinetics and dose-response effects of niacin, ultimately influencing degree of weight change from supplementation.  Additionally, since various medical conditions require prescription treatments, it is possible that the drugs will potentiate or attenuate the degree of niacin-induced weight change that you experience.
• Physical activity: The effect of niacin supplementation on weight and biological processes might differ between 2 individuals based on degree of physical activity. For example, certain studies suggest that niacin supplementation increases concentrations of growth hormone among those engaged in high-intensity exercise, whereas this effect is not seen among sedentary individuals.  In addition to the interplay between physical activity and niacin in regards to its biological effects might influence the degree of weight change that a person experiences as a result of administration.  Moreover, those who are engaged in regular physical activity may find that staying active protects against niacin-induced weight gain or enhances niacin-facilitated weight loss.

6. Niacin format

The format and specific subtype of niacin that you administer warrants consideration in regards to its affect on your body weight.  Administering an immediate-release niacin supplement may affect biological processes profoundly different than an extended-release and/or slow-release format.  Similarly, administering nicotinamide might have a different effect on your body weight than Inositol Hexanicotinate.  The most commonly utilized formats of niacin through supplementation or prescription include: standard niacin (nicotinic acid), nicotinamide (a niacin metabolite) Niaspan, Slo-Niacin, and Inositol Hexanicotinate.

• Niacin (Nicotinic acid): This is regarded as the classic, standard form of niacin sold in over-the-counter dietary supplements. It is rapidly absorbed and generally manufactured in immediate-release formats unless otherwise specified.  Nicotinic acid is likely to be fastest eliminated from a person’s system after administration.  Weight changes from nicotinic acid will likely depend on number of doses administered per day (e.g. 3 doses), as well as cumulative daily dose (e.g. 1500 mg).
• Nicotinamide: An extremely popular form of niacin purchased for supplementation is nicotinamide. Nicotinamide is a metabolite of niacin (emerging after in-vivo conversion) with a longer half-life than its parent.  It is understood that nicotinamide exerts different biological effects than standard niacin (nicotinic acid).  Research suggests that nicotinamide doesn’t cause a “niacin flush” (or many side effects of niacin) and is ineffective for cholesterol reduction.  Based on the distinct biological effects induced by nicotinamide when compared to niacin, it’s reasonable to suspect that persons supplementing with nicotinamide might experience weight changes that they wouldn’t have experienced while taking standard niacin (and vice-versa).
• Niacor or Niaspan: These are pharmaceutical medications engineered to contain high-dose niacin (vitamin B3) for the treatment of hypercholesterolemia and hyperlipidemia. The high doses of niacin within medications are suspected to upregulate HDL cholesterol and decrease LDL and total cholesterol.  It should be noted that Niacor is an immediate-release (IR) medication that contains 500 mg niacin per pill, whereas Niaspan is an extended-release (ER) medication that contains 500 mg, 750 mg, or 1000 mg per pill.  It’s possible that biological responses and corresponding weight change may differ based on whether a person uses Niacor or Niaspan.
• Slo-Niacin: This is a popular supplement with a controlled-release delivery of niacin (500 mg) through a polygel tablet. It remains unclear as to how long the release from Slo-Niacin lasts, however, it is likely that the medication is absorbed over a much longer duration than standardized immediate-release niacin.  Nevertheless, it is possible that Slo-Niacin is released over shorter duration than the pharmaceutical drug Niaspan.  The weight change that you experience from Slo-Niacin may differ slightly from Niacor and/or Niaspan as a result of the release speed and dose.
• Inositol Hexanicotinate (IHN): This is an esterified form of niacin that can be purchased over-the-counter. It consists of 6 nicotinic acid (niacin) molecules with an inositol molecule in the center of its chemical structure.  It is often marketed as “no flush” niacin and manufactured in dosages of 250 mg, 500 mg, or 1000 mg.  Most consider inositol hexanicotinate to affect biological processes differently than other forms of niacin.  Furthermore, inositol hexanicotinate is not regarded as useful for the management of hypercholesterolemia or hyperlipidemia.  Since weight gain is an inositol side effect, those using inositol hexanicotinate to attain niacin may be most prone to weight gain.

Niacin for Weight Loss? Or does it cause weight gain? (Review of Research)

As of current, no studies have investigated the direct effect of niacin intake on bodyweight and body composition in humans.  That said, the pharmaceutical drug Niaspan (niacin extended-release) manufactured by AbbVie Inc. is approved by the FDA for the management of hypercholesterolemia and hyperlipidemia – and data regarding its side effect/long-term effect profile does not suggest that it significantly alters body weight.  One might surmise that lack of weight change (loss/gain) on Niaspan could be a result of a restricted dosage range (between 1000 mg to 3000 mg) associated with treating medical conditions.

Guidelines for Niaspan dosing suggest that users should take between 500 mg and 2000 mg per day (in divided doses) to normalize cholesterol and lipids.  Based on the fact that Niaspan users are taking mega-doses of niacin each day and don’t appear to be gaining weight over a long-term, there’s not much reason to believe that niacin facilitates any sort of weight change. Nonetheless, zero randomized controlled trials have been conducted assessing the usefulness of niacin as a weight loss supplement and there’s always some unpredictable outliers who will report weight change (loss or gain) irrespective of the majority.

Included below are some studies that have discussed how niacin intake (from diet and supplements) might affect a person’s body weight.  Other studies have documented the influence of niacin supplementation on the weight of animal models.  Though we cannot extrapolate findings from animal models to humans, a majority of the research suggests that niacin is more likely to promote weight gain than loss.

2015: Vitamin paradox in obesity: Deficiency or excess?

A paper by Zhou, Li, Chen, and Zhou (2015) discuss whether individuals with obesity are deficient in vitamins or consuming excessive amounts.  Researchers mention that synthetic vitamins were engineered to enhance the nutritional value of food in the 1930s and dietary supplements were developed to help counteract deficiencies.  Unpredictably, the enhancement of food with vitamins has been correlated with skyrocketing rates of obesity, as well as associated conditions including: cancer, cardiovascular disease, and hypertension.

Another finding was that persons with obesity tend to exhibit deficits in fasting serum vitamins (e.g. folate, vitamin D, etc.) compared to non-obese counterparts.  Although fasted serum concentrations of folate in obese subjects appear deficient, erythrocyte folate levels and serum folate oxidation products are elevated.  The aforestated abnormalities in folate concentrations among individuals with obesity are hypothesized to have resulted from chronic overconsumption of folic acid, ultimately inducing overactivation of the CYP2E1 enzyme.

Of additional interest is the finding that, similar to the rapid metabolism of folate via CYP2E1, individuals with obesity exhibit expedited metabolism of niacin.  Expedited niacin metabolism occurs as a result of upregulated activity in niacin-degrading enzymes.  It is hypothesized that overconsumption of niacin (vitamin B3) over a long-term may have lead to serum deficits.

Researchers recommend considering the possibility that low fasting vitamin levels among individuals with obesity may signify chronic/excessive dietary intake – rather than suboptimal/deficient intake.  Additionally, they theorize that the excessive vitamin intake may have induced a poisoning response within the body, contributing to obesity and associated biological abnormalities.  For this reason, anyone considering supplementing with niacin for weight loss may want to reevaluate the option as it could exacerbate the already-overactive niacin-degradation, possibly facilitating weight gain and/or worsening of health.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/26322161

2012: Intravenous niacin acutely improves the efficiency of dietary fat storage in lean and obese humans.

Nelson, Vlazny, Smailovic, Miles (2012) conducted a study in which they administered niacin intravenously to 11 humans (6 lean, 5 obese).  Their aim was to determine whether niacin influences the efficiency of dietary fat storage by measuring spillover of fatty acids.  Irregularities in free fatty acid metabolism are implicated in Type 2 diabetes, insulin resistance, and dyslipidemia – each of which are associated with weight gain.

For the study, researchers intravenously administered either 2.8 mg/min of niacin OR saline solutions during continuous feeding.  Results suggested that spillover of fatty acids was reduced after intravenous niacin (2.8 mg/min) infusions compared to the saline infusion in both lean and obese participants.  It was believed that niacin decreased fatty acid spillover by exerting an anti-lipolytic effect on visceral tissue.

Keep in mind that this study was small-scale and assessed the effect of intravenous niacin on fatty acid spillover of participants during meal consumption.  It is unclear as to whether regular oral administration of niacin over an extended duration and/or at a different dose would yield similar results.  There’s reason to believe that the anti-lipolytic effect of niacin on visceral tissue may lead to weight gain.

Some researchers believe that high rates of spillover in visceral fat may limit gains in body fat.  Reducing the spillover rates via an anti-lipolytic effect (as induced by intravenous niacin) therefore could promote unwanted additional weight gain.  Unless you believe that reducing spillover of free fatty acids will help you lose weight, the evidence from this study supports the idea that it’s easier to gain body fat (and weight) with niacin than it is to lose it.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/22923472

2012: Effect of graded levels of niacin supplementation of a semipurified diet on energy and nitrogen balance, growth performance, diarrhea occurrence, and niacin metabolite excretion by growing swine.

A study by Ivers and Veum (2012) involved assessing the effect of niacin supplementation on 36 crossbred pigs over a 35-day duration.  The pigs consumed a semi-purified diet and were assessed for growth performance, symptoms of niacin deficiency, urinary excretion of niacin metabolites, and nitrogen balance.  Niacin was supplemented at dosages of 6 mg, 10 mg, 14 mg, 18 mg, 22 mg, and 44 mg per kilogram over the span of 6 treatments.

Bodyweight and feed consumption of the pigs was measured on a weekly basis.  Results indicated that niacin at 14 mg/kg resulted in better health of the pigs plus greater average daily feed intake and growth than those receiving lesser amounts.  There appeared to be no additional weight gain and/or growth performance improvements to be attained from increasing the niacin intake beyond 14 mg/kg.

The findings imply that suboptimal niacin intake may be associated with lower bodyweight and daily food consumption – as well as other health problems.  In humans, it is known that poor niacin intake can lead to pellagra, and in some cases, low body weight.  If we were to extrapolate these findings to humans, we might conclude that doses beyond a biologically useful amount have no effect on body weight.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/21873540

2011: Effect of dietary supplemental nicotinic acid on growth performance, carcass characteristics and meat quality in three genotypes of chicken.

Jiang, Zhao, Chen, et al. (2011) sought to determine the effects of nicotinic acid (NA) administered as a dietary supplement to chickens.  Specific things the researchers looked for were changes in growth performance, meat quality, and carcass characteristics.  For the study, they used 2 types of slow-growing chickens and 1 type of fast-growing chickens.

The chickens were assigned to receive either 0 mg, 30 mg, 60 mg, or 120 mg of nicotinic acid per kilogram of bodyweight.  It was noted that increasing supplementation from 0 mg to 60 mg of nicotinic acid in the slow-growing chickens increased: daily gains in weight, feed intake, intermuscular fat, thickness of subcutaneous fat, and abdominal fat percentage.  Somewhat intriguing was the finding that weight and fat gains decreased slightly at the 120 mg/kg dose compared to the 60 mg/kg dose.

In any regard, researchers believe that the weight gain from nicotinic acid was a result of toxicity.  Since the chickens received substantially more nicotinic acid than was biologically optimal, it induced dysfunction within homeostatic systems and lead to weight gain.  Although it’s difficult to compare the effects of nicotinic acid on chickens to its effect on humans, there may be similar outcomes above a particular dosage threshold.

The goal should then be to ensure that individuals are getting enough niacin, but not too much.  Excessive niacin intake (as may occur with supplementation) may interfere with preexisting weight loss efforts.  That said, its possible that niacin supplementation could facilitate weight gain among those hoping to pack on some extra pounds.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/20666866/

2010: Chronic niacin overload may be involved in the increased prevalence of obesity in US children.

Li, Sun, Zhou, et al. (2010) sought to determine whether nicotinamide (a form of niacin) might alter glucose metabolism as well as affect likelihood of obesity.  As part of their study, researchers recruited 5 healthy individuals (males, age 20-24) and conducted 2 oral glucose tolerance tests: the first involving administration of glucose (75 grams) with nicotinamide (300 mg) and the second involving glucose (75 grams) without co-administration of nicotinamide (to serve as a control).

It was noted that tests were conducted after a full night’s fast and separated with a 4-day interval.  Blood samples were collected after each test to determine concentrations of hydrogen peroxide, plasma insulin, and glucose.  Results indicated that, compared to the control (standalone glucose), the glucose plus nicotinamide (300 mg) yielded significantly greater plasma hydrogen peroxide and insulin levels at 1-hour post-administration plus substantial reductions in plasma glucose at 3-hours post-administration.

Researchers also conducted a lag-regression analysis to assess the relationship between niacin intake and obesity rates among children in the United States.  The results from their lag-regression analysis indicated that obesity rates among children in the United States were directly correlated with increased per capita niacin consumption.  It was theorized that niacin-fortified foods (e.g. grains, cereals, etc.) are a big contributing factor.

Though it cannot be proven that increased niacin is culpable for weight gain, researchers showcase that niacin supplementation affects oxidative stress, glucose, and insulin.  Moreover, their regression analysis supports the idea that elevated dietary niacin might be contributing to obesity.  They propose that niacin stimulates the appetite through oxidative stress signals, resulting in greater food consumption.  Rather than helping with weight loss, this study suggests that niacin is more likely to exacerbate weight gain.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/20480523

2009: Effects of excess nicotinic acid on growth and the urinary excretion of B-group vitamins and the metabolism of tryptophan in weaning rats.

Fukuwatari, Kurata, and Shibata (2009) sought to determine the maximum safe and/or tolerable quantity of nicotinic acid intake in humans.  For this reason, they decided to conduct a study testing the effect of excessive nicotinic acid concentrations on body weight, food intake, urinary excretion of hydrophilic vitamins, and tryptophan – in weaning rats.  The weaning rats were assigned to receive a casein diet that was either: niacin free (control) OR incorporated 0.1% nicotinic acid, 0.3% nicotinic acid, or 0.5% nicotinic acid – for a duration of 23 days.

Results indicated that excessive intake of nicotinic acid failed to alter body weight, food intake, serotonin levels (CNS / PNS), nor the concentrations of hydrophilic vitamins excreted within urine.  It was noted that rats receiving the 0.5% nicotinic acid excreted more quinolinic acid within urine, and all diets containing over 0.3% nicotinic acid resulted in elevated levels of nicotinic acid within urine – a relatively unsurprising finding.  Furthermore, no adverse effects were seen from 0.5% nicotinic acid diets, which corresponds with approximately 450 mg/kg body weight per day.

In summary, this study suggests that administering high doses of nicotinic acid (a form of niacin) for a duration of 23 days has zero effect on the bodyweight of weaning rats.  Though these results cannot be extrapolated to humans, the doses of niacin used in this study were extremely high.  Assuming humans respond similarly to nicotinic acid as the rats in this study, it’s likely that over a short-term, niacin supplementation would have no effect on bodyweight or food intake.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/19436156

2004: Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract on weight loss.

A study by Preuss, Bagchi, Bagchi, et al. (2004) sought to determine whether administration of HCA-SX ((-)-hydroxycitric acid) used as a standalone or with niacin-bound chromium (NBC) plus Gymnema sylvestre extract (GSE) affects bodyweight of obese individuals.  The study was randomized, double-blinded, placebo-controlled and conducted over the course of 8-weeks.  A total of 60 obese participants were assigned at random to one of three groups: HCA-SX (4667 mg); HCA-SX plus NBC (4 mg) and GSE (400 mg); or a placebo (t.i.d.).

Throughout the study, researchers documented body weight, BMI, appetite, lipids, leptin, and urinary fat metabolites.  It was theorized that HCA-SX would decrease appetite while simultaneously attenuating fat synthesis to reduce bodyweight.  The niacin-bound chromium (NBC) is thought to promote healthy insulin concentrations, whereas Gymnema sylvestre extract (GSE) is understood to enhance weight loss efforts and blood glucose.

It was further noted that all participants were assigned to a diet consisting of 2000 kcal per day plus engaged in daily walking (under supervision).  Results indicated that recipients of HCA-SX (standalone), as well as the combination of HCA-SX plus NBC and GSE – exhibited 5-6% body weight and BMI reductions.  The weight loss was accompanied by decreases in food consumption, LDL cholesterol, triglycerides, and serum leptin.

Despite the finding that both of the active treatment groups lost weight, there didn’t appear to be significant differences between the two, suggestive of the fact that additional supplementation with NBC and GSE may have been unnecessary.  Even if there was an additive weight loss effect, we don’t know whether it might’ve been more related to the NBC, GSE, or whether the combination of both was synergistic.  Moreover, assuming niacin-bound chromium amplified weight loss efforts, there’s only around 1.1 mg niacin in the niacin-bound chromium (with 200 mcg chromium), making it unlikely that the low dose niacin facilitated any weight loss.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/15056124

1999: Effects of niacin-bound chromium supplementation on body composition in overweight African-American women.

Crawford, Scheckenbach, Preuss (1999) conducted a study investigating the effects of niacin-bound chromium (NBC) on the body composition of 20 overweight African-American women over a 2-month duration.  In addition to NBC supplementation at a dose of 600 mcg, the women had modestly altered their diets and taken up exercising in effort to lose weight.  Initially, the women received a placebo (t.i.d.) for a control period of 2 months and were monitored for changes in body weight and composition.

Next, the women received niacin-bound chromium (200 mcg) three times per day for a 2-month duration and were monitored for changes in body weight and composition.  It should be noted that, on average, a 200 mcg niacin-bound chromium supplement contains around 1.1 mg of niacin.  For a 600 mcg per day dose (200 mcg, t.i.d.), we could estimate that women received around 3.3 mg niacin – not a very large amount.

Results indicated that niacin-bound chromium caused significant fat loss while simultaneously preserving muscle mass among the overweight women – compared to the placebo.  No significant differences in bodyweight were observed.  Even if the niacin-bound chromium appeared effective for reducing bodyweight of participants in this study, there were problems with its design and the confound of diet plus exercise.  Nonetheless, this shows that small amounts of niacin (bound to the chromium) had no effect on body weight of overweight women.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/11225649

1996: Fate of nicotinamide differs due to an intake of nicotinamide.

Shibata, Shimada, and Taguchi (1996) note that catabolism of nicotinamide (Nam) changes in response to the level of nicotinamide intake by rats.  When rats are fed with diets devoid of nicotinamide that limited tryptophan, the chief metabolite of niacin was 4-Py (N1-methyl-4-pyridone-3-carboxamide.  That said, when dietary nicotinamide intake was slightly increased, the primary metabolite excreted was N1-methylnicotinamide (MNA).

Rats fed a diet containing 0.5% nicotinamide excreted the metabolite Nicotinamide-N-oxide plus nicotinic acid and nicotinuric acid.  Researchers believed that these metabolites are likely to appear only when levels of niacin increase beyond a toxic threshold.  In addition to analyzing metabolite formation associated with nicotinamide consumption, Shibata et al. analyzed the effect of nicotinamide intake on bodyweight and food intake.

The researchers assigned rats to receive diets containing 0 mg/kg, 60 mg/kg, 1000 mg/kg, and 5000 mg/kg nicotinamide.  Results indicated that increased consumption of nicotinamide caused increases in food consumption and bodyweight.  Initial exposure to extremely high-dose nicotinamide at 5000 mg/kg inhibited weight gain due to toxicity.

Data indicated that the most significant increase in bodyweight occurred among rats receiving the 60 mg/kg, followed thereafter by recipients of the 1000 mg/kg nicotinamide.  From this research, we can hypothesize that peak weight gain from niacin intake might occur at around 60 mg/kg from the diet, but possibly significantly less (since there was no intermediary dose between 0 mg/kg and 60 mg/kg).  Although this is a rat study, it is important to consider that these findings may apply to humans.

In other words, consuming excessive dietary niacin and/or supplementing with niacin may provoke weight gain.  When considering that there’s up to 27 mg niacin in a single cup of cereal (as a result of fortification), niacin overconsumption may be more endemic than suspected in developed countries; the RDA is less than 20 mg per day.  Also accounting for the fact that most people eat more than 1 cup of cereal plus consume other foods with niacin –  the elevated niacin intake may be responsible for weight gain.

So why can people supplement with niacin or take drugs like Niaspan without experiencing weight gain?  Researchers believe that similar to the rats in the aforestated study, when niacin concentrations exceed a maximum threshold, they become toxic to the body, and this toxicity offsets weight gain.  It is theorized that toxicity manifests in the form of increased oxidative stress which is damaging to the body, but also makes the excessive niacin intake “weight neutral.”

To sum up the hypotheses made by researchers, consuming just enough niacin for biological function is healthy (e.g. the recommended daily allowance).  Exceeding the recommended daily allowance of niacin may contribute to weight gain and excessive food intake.  However, when the recommended daily allowance of niacin is exceeded beyond a certain threshold (e.g. doses of 1-3 grams in the form of a supplement), it becomes toxic to the body and has no effect upon bodyweight.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/8782418/

1993: Niacin in dairy and beef cattle nutrition.

Flachowsky (1993) reported the effects of niacin supplementation in dairy and beef cattle.  In the report, Flachowsky documents the fact that administration of niacin supplementation to cows early in lactation decreases fat mobilization, increases blood glucose concentrations, and improves milk yield by approximately 3-4%.  It was also noted that niacin supplementation reduced body weight loss during the early stages of lactation.

This shows that increasing niacin intake prevents weight loss that typically occurs in dairy and beef cattle.  That said, it is unknown as to whether this increase in body weight would be considered conducive to general health of the cattle or if it is associated with overconsumption of niacin.  If associated with overconsumption of niacin, this report would provide more evidence suggesting that increasing niacin intake beyond a certain threshold in animals and humans – leads to weight gain and/or interferes with weight loss.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/8517765

1985: The effects of increased levels of niacin supplementation on growth rate and carcass composition of broiler chickens.

Waldroup, Hellwig, Spencer, et al. (1985) tested the effect of niacin supplementation on the growth rate and body composition of broiler chickens.  It was noted that a realistic chicken diet contains 20.7-23.7 mg/kg niacin, and for this study, researchers fortified the diet with an additional 33 mg/kg niacin.  Thereafter, they assigned chickens to receive either: 0 mg/kg, 33 mg/kg, or 66 mg/kg of additional supplemental niacin.

It was noted that adding 33 mg/kg or 66 mg/kg to an already-supplemented 33 mg/kg diet lead to increased weight gain in the chickens.  That said, there was no significant effect on abdominal fat or percentage of carcass dressing.  While increased fat on chickens as a result of supplemental niacin may be healthy, it could also indicate that excessive niacin intake causes unhealthy weight gain.  Preliminary evidence suggests that too much niacin may cause weight gain in animals (rats, chickens, cattle) and humans.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/4048063

Verdict: Niacin unlikely to cause weight change in most users…

For the majority of individuals supplementing with niacin, there’s no compelling evidence to suggest that it’s likely to induce weight change [in the form of a net loss or gain].  While studies in animals such as chickens, beef cattle, rats, and mice suggest that supplemental niacin increases feeding behavior, ultimately leading to weight gain, these effects haven’t been replicated in humans.  Many supplements induce significant weight change (and/or biological effects) in animals, yet don’t affect human body weight.

Some of the research investigating the effect of niacin on body weight in animals was conducted over an extremely short-term, making it unknown as to whether weight gain would’ve continued over a longer duration.  When considering the fact that niacin’s effect on the biology of an animal is not the same as its effect within humans, it’s important to avoid extrapolating any findings suggestive of weight gain in animals to human users.  One could theorize that niacin is more likely to cause weight gain than weight loss based on findings in animals, however, this theory cannot be confirmed.

Furthermore, it is worth highlighting data from studies investigating the long-term efficacy, safety, and tolerability of pharmaceutical-grade niacin (e.g. Niaspan) for the management of hypercholesterolemia and hyperlipidemia in humans.  None of the data is suggestive of the fact that long-term, high-dose administration of niacin is likely to affect body weight or body composition of users.  While there is some evidence indicating that other adverse reactions such as hyperglycemia, insulin abnormalities, and/or hepatotoxicity may occur, these reactions aren’t automatically coupled with simultaneous weight change.

A critical analysis between excessive B-vitamin intake (including niacin) and obesity was conducted by Zhou, Li, Zhou, et al. (2014).  The authors presented a graphic showing obesity rates rising after dietary niacin intake was increased (as a result of fortification), however, the increases in obesity diagnoses lagged behind the niacin intake by 10 years.  Specifically, as dietary niacin intake increased by 60% in the United States, obesity rates doubled within the next decade.

If niacin was culpable for the skyrocketing obesity rates, it appears as though it takes a considerable amount of time (up to 10 years) for it to induce weight gain.  Based on this correlation, should we assume that supratherapeutic intake of niacin from fortified foods causes obesity over a long-term?  No.  Although it is possible that increasing niacin intake might’ve played a role in causing obesity (along with other factors), it’s causative role cannot be proven.

Even if elevated intake of niacin contributed to rising obesity diagnoses, it is extremely unlikely that the niacin is solely to blame; it may only play an extremely minor (or perhaps negligible role).  Perhaps noteworthy and suggestive of the fact that supplemental niacin does NOT cause weight gain is the fact that users of B-complex vitamins or multivitamins (which contain ~20 mg niacin) appear to be less at risk for developing obesity.  Based on this finding, we might suspect that some extra niacin could prevent weight gain or induce weight loss.

However, lower rates of obesity among B-complex and multivitamin users may not necessarily be attributed to the niacin.  It is possible that users of vitamins are more health conscious than the general population, and even if niacin were to cause weight gain, these individuals would find ways to reduce it (e.g. with extra exercise or caloric restriction).  Also, it is possible that the other vitamins included within a multivitamin or B-complex cancel out the long-term effects of niacin on biological processes that may facilitate weight change.

Should we assume that niacin exerts an analogous effect on human body weight as it does within animals, it’s likely that weight change is contingent upon the dosage of niacin ingested on a regular basis.  In animals, it seems as though niacin supplementation promotes peak weight gain up to a certain supratherapeutic dose, but administering a significantly larger quantity than the dose associated with peak weight gain yields weight neutrality or weight loss.  In other words, supplementation with low-to-moderate doses (50 mg to 1000 mg) might cause weight gain, whereas greater doses (1000 mg to 3000 mg) may have no effect on body weight.

It is worth noting that a study by Li, Sun, Zhou, et al. (2010) discovered that doses of nicotinamide at 300 mg significantly increases oxidative stress (plasma hydrogen peroxide) and insulin levels within 1-hour of administration, and blood glucose plummets 3-hours after administration, possibly indicative of hypoglycemic states in which an individual may experience an increase in appetite whereby they consume more food.  Despite this finding, there is no clear evidence indicating that niacin supplementation causes weight change in humans.  Those suspecting that niacin is responsible for their substantial weight loss or weight gain may want to reconsider and account for other factors.

Then again, the degree to which niacin alters a person’s body weight might be subject to individual variation based on numerous aforestated variables such as: dosage and format of niacin, duration of supplementation, genetics, co-administered substances, etc.  To accurately determine whether niacin affects your body weight over a moderate-term, you could conduct a self-experiment in which you administer either niacin or a placebo daily for several months, and then receive the opposite for another few months – all while recording weight changes.  Keep in mind that if you conduct the self-experiment, it’s recommended to confirm the safety of your plans with a medical professional prior to implementation.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/20480523

Have you tried niacin for weight loss?

If you’ve taken niacin supplements, share whether you lost weight, gained weight, or remained relatively weight neutral – in the comments section below.  To help others get a better understanding of how niacin supplementation affected your bodyweight, provide some additional details including:  how long you’ve been taking niacin (e.g. 3 months), the amount of weight fluctuation (e.g. 10 lbs), the dosage of niacin you used (e.g. 1000 mg/day), the format of niacin (e.g. Niaspan), as well as the manufacturer of your particular product.  On a scale of 1 to 10 (with “1” being least effective and “10” being highly effective), what rating would you assign to niacin as a weight loss supplement?

Assuming you’re convinced that niacin helped you lose weight, do you have a theory regarding its mechanism of weight loss action?  Furthermore, if you lost weight while taking niacin, have you considered confounds such as:  caloric restriction, dietary modifications, increased physical activity (caloric expenditure), and other substances (drugs/supplements) – as playing a role in the weight loss?  How can you confirm that you wouldn’t have lost more weight without the niacin supplementation than you did while taking it?

For those that remain confident that niacin was a prominent inducer of their weight loss, how much time did it take for substantial weight loss to occur?  Has the weight loss dwindled, plateaued, or remained constant over an extended duration of time?  The bottom line is that while some may think niacin somehow speeds up the metabolism or flushes out “fat cells,” there’s no evidence to support this theory.  Overall, it doesn’t seem as though niacin is likely to significantly affect bodyweight, however, there’s more evidence to suggest that it promotes weight gain than weight loss – especially when taken over a long-term.

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