Tag: niacin

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Kale and carrots – super good right? maybe not for everyone.

The take home point about retinoid toxicity that is mind blowing to this dietitian (last post, & second half of this post) is that kale and carrots and other super nutritious beta-carotene rich foods might be part of the health problem for some people. If retinoid toxicity is occurring due to an enzyme change in the liver then the long held belief that we can’t really overdose on the carrot type of vitamin A may be wrong. Carnivore diet followers though, don’t rejoice too quickly, the animal product foods are sources of the active form of vitamin A and would definitely be part of the problem if excessive retinal was being activated to retinoic acid.

Thanks to everyone who responded to my survey on retinoid toxicity (last post/document). The summary points are that dry skin, seasonal allergies, and fibromyalgia type fatigue are fairly common symptoms and 100% of respondents (including me) were unfamiliar with all of the symptoms. Rewriting the survey and getting approval for research is needed. The initial effort did show that the topic is an unfamiliar one.

Change in the gene expression of enzymes involved in retinal/retinoic acid metabolism has been seen with infection with the Epstein Barr virus. (11) Chronic symptoms for years after an Epstein Barr infection have been known. The range of symptoms that can be due to retinoid toxicity could confuse the diagnosis process – see a dermatologist for the skin, an autoimmune/allergy specialist and a general practitioner might also be involved – would any one of them ask about all the possible retinoid toxicity symptoms? or suggest cutting back on food and supplement sources of vitamin A/beta carotene in order to just test the theory and see if any symptoms improve?

Retinoid toxicity may also help explain why smoking tobacco seems to have a somewhat protective effect against peripheral neuropathy while also being a risk – NAD+ deficiency could mean nicotine is helping provide a source of niacin – so the take home point there would be take niacin to help prevent nerve damage and fatigue (1, 2, 3) without providing smoke toxins that also worsen health risks. (post: Neuropathy can be a cause of extreme tiredness)

Nicotinamide adenine dinucleotide (NAD+)  is an essential pyridine nucleotide involved in energy production within the mitochondria of cells and is protective against harmful effects of oxidative stress ( 2) – the chemical effects of physical or emotional stressors on the body. NAD+ is used in one enzyme involved in vitamin A metabolism. (9)

The following video connects Mast Cell over activity with niacin deficiency. Retinoic acid would add to mast cell activity as it is an activator of mast cells too. Mast cells can release histamine & then there can also be more supplied from foods, or produced in response to foods in mast cells in the intestinal lining. If the Epstein Barr virus causes retinoic acid metabolism gene changes maybe other infections can too. See: First Effective Treatment for Long Covid | Stunning Data from Huge New Study Dec 22, 2020 youtube.com, https://youtu.be/9-3V3h0ncIA  

  • Low histamine/MCAS protocol
  • Niacin, zinc, selenium, vitamin C, D, quercetin, magnesium. – Dr. Ade Wentzel 
  • Anti-histamine medications, over-the-counter generally
  • Prescription medications. Possibly ACE1 and ACE2 blockers, or Mast cell stabilizers or inhibitors.

The chemistry is complex, I am still learning, in the meantime though, cutting back on my daily intake of carrots, kale and then the addition of a lot of mango for a while – DID HELP – when did I ever think that I might be eating too much kale? or mango or my favorite anti-cancer vegetable – the carrot? answer – never. Learning about retinoid toxicity has been unexpected but helpful. Again carnivore diet fans – earlier in my symptom flare up history I found I had to cut out all animal products from my diet in order to get the new skin problem to resolve. Retinoid toxicity may have been a factor that I reduced without realizing why it helped but it worked so I stuck with it.

From a differential diagnosis perspective the range of symptoms that can be a result of retinoid toxicity would likely not be connected to each other. The patient might be seeing an allergy and autoimmune specialist, a psychiatric medical professional and talk therapist, and a general practitioner and as problems worsened a liver specialist, kidney specialist, and a neurologist might be added to the medical team – would they all talk to each other about the amount of carrots and liver in the patient’s average daily diet?

Probably not.

Updates are likely. Document with previous work on MCAS & a copy the survey.

Happy New Year’s Eve Eve!

Celebrating a new year and new health discoveries! (image: fireworks)

Excerpt from previous post – sources/types of vitamin A & retinoic acid

Might an excess or retinoic acid be overstimulating activity in the brain and causing hyperexcitability? (1, 2) Excess retinoic acid can have negative effects in the brain, particularly the hippocampus, (6), the area damaged initially in Alzheimer’s dementia, and may cause cell death. (7)

“The three active forms of vitamin A in the body are retinol, retinal, and retinoic acid.” … “Retinol and retinyl esters are often referred to as preformed vitamin A. Retinol can be converted by the body to retinal, which can be in turn be oxidized to retinoic acid, the form of vitamin A known to regulate gene transcription. Retinol, retinal, retinoic acid, and related compounds are known as retinoids. β-Carotene and other food carotenoids that can be converted by the body into retinol are referred to as provitamin A carotenoids (see the article on Carotenoids). ” (11)

Malfunction of CYP enzymes could increase the risk of excess retinoic acid as they are required to break down the active forms of vitamin A. (12)

Beta-carotene food sources

Beta-carotene, is an inactive form of vitamin A that is generally considered non-toxic, it provides the orange color of carrots, and since it is a fat soluble nutrient it can collect within our skin if eaten in excess and cause an orange color to the skin. (8, 13) It is unlikely to eat enough of the nutrient to cause the skin color change unless regularly drinking juice made with carrots, or kale or other fruits and vegetables that are very rich in beta- carotene. It is unlikely to cause any health problems other than to appear orange for a while (stop drinking so much carrot juice to make it fade). Infants and toddlers who are fed limited numbers of foods but daily may also develop the problem if carrots and sweet potatoes are given consistently instead of including more variety.

Beta-carotene may be broken down to the active retinal form in the intestinal lining or in the liver. (13)

Sources of Pre-formed vitamin A and Provitamin A – beta-carotene and other carotenoids.

“…vitamin A toxicity can occur from either topical or oral use. Oral vitamin A delivery comes in two forms: provitamin A (a prodrug that is metabolized to vitamin A) and preformed vitamin A. Pre-formed vitamin A is obtained from animal food sources, including dairy products and liver, and in most supplements. A list of other foods containing Vitamin A includes milk, cheese, margarine, butter, eggs, chicken, chicken liver, beef, beef liver, processed meats, pizza, fish, and cold breakfast cereals[1]. Provitamin A (beta-carotene and other carotenoids), found in plants such as green leafy vegetables, sweet potatoes, and carrots, must be metabolized to vitamin A. As a result, it is less likely to cause toxicity.” (9) [See Reference list from previous post/document)

From the survey:

  1. Meals and snacks include meats, poultry, fish, milk and other dairy products. [and Vitamin A & D fortified milk equivalent drinks]
    1. Several servings per day typically
    2. At least one serving per day
    3. At least one serving per week
    4. One serving per month or less
    5. No servings of animal products typically
    6. Unknown
  2. Meals and snacks include carrots, tomato products (fresh, or tomato sauce, ketchup, or salsa), sweet potatoes, winter squash or pumpkin, dark green leafy vegetables, cantaloupe, apricots, mango, papaya, peaches, nectarines.
    1. Several servings per day typically.
    2. At least one serving every other day
    3. At least one serving per week
    4. One serving or less per month
    5. No servings of carotenoid rich plant foods typically

*2. Answer 2 is the amount menu planners have as a minimum goal – 1 beta carotene rich produce serving at least every other day.

My own symptoms & diet: I was having several servings of beta carotene rich foods daily and often several times a day, when I had a skin symptom flare up, reducing to the less frequent use helped the skin problem, cheilitis, finally get better. Cheilitis is nonhealing cracks/fissures at the corners of the lips and my problem didn’t get better with more vitamin Bs or iron which deficiencies of can also be a cause., but then got better within a few days of stopping the daily carrot, kale and mango intake. I have one serving occasionally now instead of several daily.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List – includes excerpts & references not mentioned in the text.

  1. Steve Hill, Niacin Increases NAD+ Significantly in Human Trial. June 8, 2020, lifespan.io, https://www.lifespan.io/news/niacin-increases-nad-significantly-in-human-trial/
  2. Braidy N, Villalva MD, van Eeden S. Sobriety and Satiety: Is NAD+ the Answer?. Antioxidants (Basel). 2020;9(5):425. Published 2020 May 14. doi:10.3390/antiox9050425 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278809/
  3. Griffith GD, Griffith T, Byerrum RU, Nicotinic Acid as a Metabolite of Nicotine in Nkotiana rustica.* J of Biological Chemistry, Vol. 226, No. 12, December 1960 https://www.jbc.org/content/235/12/3536.full.pdf “It appears that the nicotinic acid derived from nicotine enters the metabolic pool and presumably is converted to bound forms such as the pyridine nucleotides, since the dilution of isotope increases somewhat with time.“
  4. Nicotinic acid – an overview. sciencedirect.com https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/nicotinic-acid Niacin, V.K. Lule, … C.D. Khedkar, in Encyclopedia of Food and Health, 2016, https://www.sciencedirect.com/science/article/pii/B9780123849472004839 Interactions of Niacin with Drugs: “Taking nicotinic acid and/or nicotinamide and using a nicotine patch can increase the possibility of becoming flushed and dizzy.” – may increase the risk of the niacin flush reaction, also a side effect risk of the nicotine patch:
  5. Niacin and Niacinamide (Vitamin B3) , webMD.com, https://www.webmd.com/vitamins/ai/ingredientmono-924/niacin-and-niacinamide-vitamin-b3
  6. Pirinen E, Auranen M, Khan NA, Brilhante V, Urho N, Pessia A, Hakkarainen A, Kuula J, Heinonen U, Schmidt MS, Haimilahti K, Piirilä P, Lundbom N, Taskinen MR, Brenner C, Velagapudi V, Pietiläinen KH, Suomalainen A. Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metab. 2020 Jun 2;31(6):1078-1090.e5. doi: 10.1016/j.cmet.2020.04.008. Epub 2020 May 7. Erratum in: Cell Metab. 2020 Jul 7;32(1):144. PMID: 32386566. https://pubmed.ncbi.nlm.nih.gov/32386566/
  7. Luis Rajman, Karolina Chwalek, and David A. Sinclair https://www.cell.com/cell-metabolism/pdf/S1550-4131(18)30122-0.pdf “NMNATs are also attractive targets for raising NAD+ in cells because they have dual substrate specificity for NMN and nicotinic acid mononucleotide (NaMN), and they contribute to both de novo and salvage pathways (Zhou et al., 2002). The green tea compound epigallocatechin gallate has been reported to activate NMNAT2 by more than 100% and NMNAT3 by 42% at 50 mM, although this needs to be confirmed, as no data were presented in the paper (Berger et al., 2005). … An alternative approach to raising NAD+ is to inhibit its degradation either by inhibiting PARPs or NADases, also known as glycohydrolases. The major NADase in mammals, CD38, is inhibited in vitro at low micromolar concentrations by flavonoids including luteolinidin, kuromanin, luteolin, quercetin, and apigenin (IC50 < 10 mM) .” …niacin/niacinamide supp may help reduce risk of kidney injury which involves low NAD+ … bloodflow and muscle and nerve function also may be improved by adequate niacin treatment. … “Since then, numerous studies have reinforced the view that NAD+ levels are key to neuronal function and survival. This includes the dependence on NMNAT2 and its NAD synthesis activity for axonal survival (Yan et al., 2010). ” Supplementing may help protect against Parkinson’s Disease and Alzheimer’s dementia and other neurologic conditions. “NAD-boosting regimens prevent and in some cases can reverse neuronal degeneration associated with hearing loss, prion toxicity, retinal damage, traumatic brain injury (TBI), and peripheral neuropathy (Brown et al., 2014; Dutca et al., 2014; Hamity et al., 2017; Lin et al., 2016; Vaur et al., 2017; Yin et al., 2014; Zhou et al., 2015) ” https://www.cell.com/cell-metabolism/pdf/S1550-4131(18)30122-0.pdf
  8. Fricker RA, Green EL, Jenkins SI, Griffin SM. The Influence of Nicotinamide on Health and Disease in the Central Nervous System. Int J Tryptophan Res. 2018;11:1178646918776658. Published 2018 May 21. doi:10.1177/1178646918776658 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966847/
  9. Seung-Hye Hong, Ho-Phuong-Thuy Ngo, Hyun-Koo Nam, Kyoung-Rok Kim, Lin-Woo Kang, Deok-Kun Oh. Alternative Biotransformation of Retinal to Retinoic Acid or Retinol by an Aldehyde Dehydrogenase from Bacillus cereus, Applied and Environmental Microbiology Jun 2016, 82 (13) 3940-3946; DOI: 10.1128/AEM.00848-16 https://aem.asm.org/content/82/13/3940 “This enzyme converted not only small aldehydes to carboxylic acids but also the large aldehyde all-trans-retinal to all-trans-retinoic acid with NAD(P)+.“
  10. 1.1.1.105: all-trans-retinol dehydrogenase (NAD+). https://www.brenda-enzymes.org/all_enzymes.php?ecno=1.1.1.105&table=Natural_Substrates_Products Epstein-Barr virus lytic infection induces retinoic acid-responsive genes through induction of a retinol-metabolizing enzyme, DHRS9.17244623 From table https://www.brenda-enzymes.org/enzyme.php?ecno=1.1.1.105&onlyTable=Disease
  11. Jones RJ, Dickerson S, Bhende PM, Delecluse HJ, Kenney SC. Epstein-Barr virus lytic infection induces retinoic acid-responsive genes through induction of a retinol-metabolizing enzyme, DHRS9. J Biol Chem. 2007 Mar 16;282(11):8317-24. doi: 10.1074/jbc.M608667200. Epub 2007 Jan 22. PMID: 17244623. https://www.jbc.org/content/282/11/8317.long “Abstract: Lytic Epstein-Barr virus (EBV) replication occurs in differentiated, but not undifferentiated, epithelial cells. Retinoic acid (RA) induces epithelial cell differentiation. The conversion of retinol into its active form, retinoic acid, requires retinol dehydrogenase enzymes. Here we show that AGS gastric carcinoma cells containing the lytic form of EBV infection have enhanced expression of a gene (DHRS9) encoding an enzyme that mediates conversion of retinol into RA. DHRS9 expression is also increased following induction of lytic viral infection in EBV-positive Burkitt lymphoma cells. We demonstrate that the EBV immediate-early protein, BZLF1, activates the DHRS9 promoter through a direct DNA binding mechanism. Furthermore, BZLF1 expression in AGS cells is sufficient to activate DHRS9 gene expression and increases the ability of retinol to induce the RA-responsive gene, CYP26A1. “
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Niacin

Niacin (vitamin B3, niacinamide, and nicotinic acid):

Copy of Food Sources of Vitamin B6 include- fortified cereal, barley, buckwheat, avocados, baked potato with the skin, beef, poultry, salmon, bananas, green leafy vegetables, beans, nuts, sunflower seeds. (2)Food Sources of Niacin include:
  • nutritional yeast;
  • meats, salmon and tuna;
  • beans, green peas;
  • peanuts, and seeds;
  • avocado, mushrooms, green leafy vegetables;
  • grains, nixtamal flour, & fortified cereals;
  • milk, coffee and tea.
Symptoms of Niacin (Vitamin B3) Deficiency:

Digestive symptoms of less severe niacin deficiency may include nausea and vomiting and may also be able to be seen visibly as an unusually bright red tongue. Several B vitamins can cause changes in the appearance of the tongue as the cells all along the digestive tract need to be replaced frequently with new cells. The B vitamins work together as a group and many are essential for the growth of new cells. See the excerpt in the reference section for other B vitamins necessary for maintaining a healthy tongue.

Headache, apathy, memory loss, disorientation, and/or depression may be neurological symptoms that occur if niacin deficiency continues long term. Fatigue may also be a symptom of niacin deficiency.

Severe niacin deficiency is called pellagra. Symptoms of pellagra include skin rashes, (dermatitis), diarrhea, dementia, and eventually death if adequate niacin isn’t provided to the patient.

The condition was discovered in groups of people who lived primarily on a diet of corn or sorghum.  However the condition was not common in Mexico, in Central America, or for some groups of Native Americans. Corn in those areas was first soaked in an alkaline solution of lime or wood ash before being made into a type of flour called nixtamal.  The alkaline soaking method makes more of the grain’s niacin content available for absorption in the human digestive system.

Nixtamal flour is available to the home shopper and might be called tortilla or tamale flour. The ingredient list would include lime or wood ash if the product was made with the alkaline presoaking step.

The amino acid, tryptophan, can be converted to niacin within the body if adequate B6, folate and heme are available (an iron rich enzyme cofactor).

Background history regarding nicotinic acid, niacin, and nicotine:

Nicotinic acid and nicotine from tobacco cigarettes have similar names because they are similar chemicals but are not the same chemical and don’t have the same function within the body. This is a content marketing issue, read more – including the comments in the following link.

A summary: Nicotinic acid is a chemically reasonable name for the form of the nutrient that was initially discovered, but the similarity of the word to nicotine made people fearful when it was first added to foods and food labels as a new nutrient fortification being added to help prevent and treat pellagra. The use of a different form with a name change to “niacin” may have been a move at that time towards a form with a more commercially successful name even though it is not as descriptive of the way the chemical is formed as the name “nicotinic acid.”

Warning – non-harmful “Niacin flush” may occur with Nicotinic acid:

For some people, excessive supplementation with the nicotinic acid form of vitamin B3, but not the niacin form, may cause a temporary non-life-threatening reaction that may include symptoms of itching, a temporary flushing or reddening of the skin, nausea and vomiting. The reaction may be referred to as a “niacin flush.” A holistic practitioner describes the reaction in the following article and mentions that it usually goes away after a week of taking the supplement and that drinking some extra water during the sensation might help ease symptoms. The practitioner suggests that the reaction may be helpful for multiple sclerosis.

Niacinamide is a form of niacin that does not help reduce cholesterol

Niacin can be converted to niacinamide in the body and both forms are available as supplements which could help prevent deficiency symptoms. However niacin may also be helpful with blood lipid (fats) levels. It may help reduce elevated levels of triglycerides which may help prevent high cholesterol levels. Niacinamide is a form that does not affect blood lipid levels and wouldn’t be recommended over the niacin form if the goal is protecting cardiovascular (heart & blood vessel) health.  http://www.webmd.com/vitamins-supplements/ingredientmono-924-niacin%20and%20niacinamide%20vitamin%20b3.aspx?activeingredientid=924&

B vitamins essential for health of the tongue (and Gastrointestinal tract):

Deficiency of several of the B vitamin group can cause changes in the appearance and surface texture of the tongue. B vitamins that can cause changes in the tongue are mentioned in the following excerpt and include “niacin (B3), riboflavin (B2), pyridoxine (B6), folic acid (folate/B9), and vitamin B12”:

  • “Deficiencies of niacin, riboflavin, pyridoxine, folic acid, or vitamin B12,  resulting from poor diet or from the administration of antagonists, may cause a sore, beefy-red tongue without a coat. In the chronic vitamin deficiency state, the tongue may become atrophic and smooth.”                   – “The Tongue – Clinical Methods – NCBI bookshelf  https://www.ncbi.nlm.nih.gov/books/NBK236/

  • See the post on Vitamin B6 for more information about how the group of B vitamins work together in energy metabolism and cell growth.
Reference used for food sources & symptoms of Niacin deficiency:
Other References used for the food sources of Niacin:

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.