Tag: mitochondria

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Niacin may help prevent or treat migraines.

Niacin may help prevent migraines or tension-type headaches when taken daily based on a review of nine articles about niacin use and migraines or tension-type headaches. It may also help end a migraine that is occurring with the cooling effect that follows the skin-reddening niacin flush.

  • The treatment of migraines and tension-type headaches with intravenous and oral niacin (nicotinic acid): systematic review of the literature. (1)

“Chronic tension-type headaches are also associated with cerebrospinal pressure or intracranial venous pressure (or both) [26]. In fact, tension-type headaches are more similar to migraine headaches than they are dissimilar, in that they seem to progress into migraine headaches due to an escalating pathophysiological process [27].” (1)

Niacin may also help reduce a migraine that is occurring, with a 500 mg dose taken to cause the niacin flush.

Regarding one of the articles reviewed: “In this [self] report, Hall describes the use of niacin for his migraine headaches remarking that the migraines resolved when intense flushing occurred.” (1)

The vasodilation in the skin that causes the warm feeling and reddening of the skin is followed by a vasoconstriction and cooling effect on the body and brain. Older research confirmed vasoconstriction in the brain occurs as well as in the peripheral blood vessels, however current research is needed. (1)

From the Discussion section (1) : “When taken intravenously or orally, niacin causes cutaneous flushing that might abort the acute symptoms of migraine by vasodilating the intracranial vessels, thus preventing the subsequent vasoconstriction of the extracranial vessels.

There is evidence that niacin is an effective peripheral vasodilator, but its ability to influence central mechanisms (i.e., cerebral blood flow and cranial hemodynamics) involved in migraine headaches have not been well studied. Niacin causes peripheral vasodilation and cutaneous flushing by inducing the production of prostaglandin D2 (PGD2) in the skin, leading to a marked increase of its metabolite, 9α, 11β-PGF2, in the plasma [22].

When niacin is administered orally in amounts of 500 mg or topically via a 6-inch patch of 10-1 M aqueous methylnicotinate on the forearm, PGD2 is markedly released in the skin and its metabolite appears in high amounts in the plasma [22, 23]. It is not known if PGD2 causes vasodilation of the intracranial arteries, but niacin’s ability to abort acute migraine headaches suggests that this might be what is occurring.

Old reports cited by Bicknell and Prescott [24], demonstrate that niacin does indeed cause vasodilation of the cerebral and spinal vessels, and that intravenous administration increases the rate of intracranial blood flow in human beings for 20–60 minutes without any significant change in blood pressure. Unfortunately, there have not been more recent reports examining the effects that niacin has upon cerebral blood flow in human subjects.” (1)

Niacin (B3) is needed for Mitochondrial function…

…so are riboflavin (B2), other B vitamins; many trace minerals including magnesium; amino acid derived creatine and cysteine; and the internally made antioxidants CoQ10, glutathione and alpha-lipoic acid.

Niacin helps mitochondria function to burn glucose for energy use or to release as heat (such as in brown fat). Riboflavin and coenzyme Q10 and other nutrients are also used by the mitochondria. (1)

“A deficit of mitochondrial energy metabolism may play a role in the pathogenesis of migraine. Since niacin improves mitochondrial energy metabolism by increasing substrate availability to complex I, it might also be an effective agent for migraine prevention.” (1)

Citric Acid Cycle – used for aerobic glycolysis of glucose by the many many Mitochondria within all of our cells.

Graphic (via Dmitry Kats, PhD, @NiacinisHealth) shows the many nutrients that are used in the Citric Acid Cycle by mitochondria when they are metabolizing glucose aerobically, with oxygen, as typical of their normal function. Anaerobic glycolysis, fermentation of glucose or glutamate without oxygen, by mitochondria is associated with cancerous cells.
Nutrients include: B1 (thiamin), B2 (riboflavin), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B7 (biotin), B9 (folate), Mg++ (magnesium), Mn++ (manganese), K+ (potassium), zinc, iron, copper, sulfate, CoQ10, carnitine, cysteine, glutathione, Lipoic acid.

B vitamins are very important and we need them in balance because they work as a team. Niacin might not help as much if there is significant lack of the other B vitamins or some of the minerals, amino acids or antioxidants needed for the Citric Acid Cycle to function. The nutrients mentioned as cofactors for the chemical reactions in the above graphic include:

  • B vitamins: B1 (thiamin) (3) , B2 (riboflavin) (4), B3 (niacin) (8, 10), B5 (pantothenic acid) (5), B6 (pyridoxine) (6, 7), B7 (biotin), B9 (folate) (9),
  • Minerals (17): Mg++ (magnesium) (11, 12, 13), Mn++ (manganese), K+ (potassium) (13), zinc (14, 15), iron (16), copper, sulfate,
  • Amino acids: carnitine (derived from lysine), cysteine,
  • Antioxidants: CoQ10, glutathione, alpha-Lipoic acid (ALA).

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

  1. Prousky, J., Seely, D. The treatment of migraines and tension-type headaches with intravenous and oral niacin (nicotinic acid): systematic review of the literature. Nutr J4, 3 (2005). https://doi.org/10.1186/1475-2891-4-3 https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-4-3
  2. Dmitry Kats, PhD, @NiacinisHealth Citric Acid Cycle graphic
  3. Thiamin: people with anorexia or alcoholism are more at risk for vitamin B1 deficiency. Aug 21, 2013 https://transcendingsquare.com/2013/08/21/thiamin/
  4. Riboflavin – Vitamin B2, May 23, 2018, https://transcendingsquare.com/2018/05/23/riboflavin-vitamin-b2/
  5. Pantothenic Acid – vitamin B5, May 24, 2018 https://transcendingsquare.com/2018/05/24/pantothenic-acid-vitamin-b5/
  6. Vitamin B6, https://transcendingsquare.com/2013/08/21/vitamin-b6-2/
  7. Pyroluria, anxiety and deficiency of B6 and zinc, most recent update, 4/9/2017 https://transcendingsquare.com/2014/09/22/pyroluria-anxiety-and-deficiency-of-b6-and-zinc/
  8. Niacin, & early treatment in general for SARS-CoV-2 is sensible, reduces hospitalization and mortality rate. https://transcendingsquare.com/2021/01/22/niacin-early-treatment-in-general-for-sars-cov-2-is-sensible-reduces-hospitalization-and-mortality-rate/
  9. Folate is essential and Folic Acid is commonly available. Aug 21, 2013, https://transcendingsquare.com/2013/08/21/folate-and-folic-acid-2/
  10. Niacin, Aug 21, 2013, https://transcendingsquare.com/2013/08/21/niacin/
  11. To have optimal Magnesium needs Protein and Phospholipids too. July 20, 2018, https://transcendingsquare.com/2018/07/20/to-have-optimal-magnesium-needs-protein-and-phospholipids-too/
  12. Magnesium – essential for eighty percent of our body’s chemistry. July 1, 2019, https://transcendingsquare.com/2019/07/01/magnesium-essential-for-eighty-percent-of-our-bodys-chemistry/
  13. Electrolytes are essential, magnesium helps protect brain cells. Feb 10, 2011, https://transcendingsquare.com/2011/02/10/electrolytes-r-us-magnesium-saves-brain-cells/
  14. Zinc, https://jenniferdepew.com/zinc
  15. Zinc and the immune system, https://www.peace-is-happy.org/post/zinc-and-the-immune-system
  16. Iron and anemia of chronic inflammation. https://www.peace-is-happy.org/post/iron-and-anemia-of-chronic-inflammation
  17. Trace Minerals – It’s Teamwork. https://www.peace-is-happy.org/post/trace-minerals-it-s-teamwork
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It is not a coincidence that my phospholipid rich diet overlaps with the Nrf2 promoting foods

The punchline – phospholipids are the building block of cannabinoids which are also a phytonutrient that causes an increase in production of Nrf2. (1, 3) The most concentrated source of cannabinoids or phospholipids is found in medical marijuana or the non-euphoric CBD oil which is more likely to be available legally. However there are other legal sources of phospholipids and cannabinoids. The phytonutrients are also found in cocoa beans/baking cocoa/dark chocolate (processing reduces the concentration and availability of the ‘bitter’ tasting nutrients in more processed milk chocolate and chocolate syrup.) Phospholipids add a slight bitter taste to foods which I’ve always been able to taste and tend to prefer. A genetic screening did find that I have a double/ both sets of genes/ difference in my ability to make any chemical with phosphorus – the phospho- part of phospholipids which are important in many chemicals in the body not just cannabinoids. (4 – an open access textbook on phosphorylation)

For example the original Lemonhead TM candies have more flavor to me than the more recent version of lemon flavored Chewy Lemonhead, (lemonhead.com). Bitterness is something we have a specialized set of tastebuds to detect. Our tastebuds have a few specific types and there are some that detect sweet, salty, sour, bitter, and some for Umami (fermented protein/free amino acid/a hint of soy sauce like flavor). Recently reseachers have suggested a set detect starch but sweet is also a starch so it might be similar to the sweet detecting tastebuds. The article explains that the difference between simple sugars and complex, longer chain carbohydrates called polysaccharides, can be detected suggesting there are two types of carbohydrate sensing tastebuds. (2)

Our sense of smell adds a lot more differences to our enjoyment of foods and beverages. Terpenes are particularly good smelling and other phenolic compounds also add aroma. Cinnamon and vanilla, basil, oregano and lemon are all sources of phenolic compounds or terpenes. These were discussed in more detail in the recent post on Nrf2 and diet tips for promoting Nrf2. It is a protein that causes genes that make important antioxidants to become active so it helps protect us against damage from oxidative stress which can be caused by health factors or by real world worries whether an upsetting conversation or bad traffic.

Pomegranate seeds (not the juice) and pumpkin seed kernels are also good sources of phospholipids. The spice cardamom powder is also a good source. See the section The DASH Diet and Pumpkin Seeds on the home page of my other website: effectivecare.info. A salad recipe and more information about genetics and cannabinoids are also available on that site or in the post Is it Starvation or Addiction?

Pomegranate extract has been studied in animal based research to examine in more detail how it helps hypertensive blood pressure problems and reduce oxidative stress. The mechanism was found to involve increasing Nrf2. The formation of mitochondria increased, and their function improved. Before treatment the hypertensive animals had fewer of the specialized proteins that are involved in production of mitochondria. Mitochondria are the cellular organelles primarily responsible for turning blood sugar/glucose into usable energy. (5)

This study uses a pomegranate extract that incorporates the peel, seeds and juice as all contain the bioactive phytonutrient, punicalagin, thought to be most helpful for anti-inflammatory, anti-tumor and anti-diabetic effects. The animals who received the extract were found to have better blood pressure, reduced heart hypertrophy ( a sign of worse heart health) and a lower heart rate. Neuronal/nerve cell activity and oxidative stress markers were decreased in the experimental treatment group compared to the control group which received a saline solution and no pomegranate extract. Angiotensin converting enzyme which is involved in blood pressure control was lower in the experimental group  that received pomegranate extract and may be the mechanism for the lower blood pressure. Pro-inflammatory cytokines were reduced in the experimental group after treatment, an indication that hypertensive inflammation was reduced. The pomegranate extract treatment led to increased levels of phosphorylated AMPK which then leads to an increase in Nrf2 and its resulting increases in antioxidant proteins which protect against injury and inflammation from oxidative stress chemicals. (5)

Pomegranate is referred to as an ancient fruit in a research study on its benefits against hepatocellular carcinoma. Spoiler alert – it was found beneficial. (6)

“PE (Pomegranate Extract) treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC (Hepatocellular Carcinoma).” (6)

One to ten grams per kilogram (1 to 10 g/kg) (6) gives us a quantity but that is of the extract which is made with the juice, seeds and peel. The inner peel is whitish in color while the outer peel is vibrantly colored similarly to the juice. An average adult weighs somewhere around 70 kg (68 kg ~ 150 pounds) so the animal study used an equivalent of 70 to 700 grams of pomegranate extract. Five grams is about a teaspoon so 70 grams would be slightly less than 5 Tablespoons or about 1/4-1/3 cup which is roughly a half a pomegranate worth of seeds with the juice and would be a reasonable serving size. Ten times that would be more than a typical serving at approximately two and a half to three and a third cups of pomegranate extract per day, for 22 weeks (6) – but if you have Hepatocellular Carcinoma that might sound good compared to other chemotherapy treatments.

My health and anxiety seems to be improved with a half a pomegranate worth of the seeds per day, or half in the morning and half in the evening when anxiety is worse. I have not tried using any part of the peel or interior whitish colored membranes so I don’t know what how edible they would taste. Pumpkin seed kernels are a higher fat food and the serving size is about 2 to 4 tablespoons, 1/8 to 1/4 cup as a snack my themselves or sprinkled on a salad. I prefer to have some of both foods every day. As well as other dark green leafy vegetables and herbs, beans, rice, nuts and other seeds, and ground lemon powder and/or lime or lemon juice. One healthy food alone isn’t enough to improve my health and mood on it’s own however the half a pomegranate can improve my mood when I’m having a worse anxiety moment. Pumpkin seed kernels are a higher fat and protein substance and don’t seem to have the quick acting mood lifting effect but I notice when I run out of them and don’t have any for a few days.

Regarding the “ancient fruit” reference in (6), yes pomegranate is mentioned in the Bible, Old Testament; 1 Samuel 14.2, “Saul was staying in the outskirts of Gibeah under the pomegranate tree…” and Old Testament; Haggai 2.19: “Is the seed yet in the barn? Do the vine, the fig tree, the pomegranate, and the olive tree still yield nothing? From this day on I will bless you.” (7)

Menu tips to be continued later, Happy holidays!

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.

  1. Li X., Han D., Tian Z., Gao B., Fan M., Li C., Li X., Wang Y., Ma S., Cao F.,

    Activation of Cannabinoid Receptor Type II by AM1241 Ameliorates Myocardial Fibrosis via Nrf2-Mediated Inhibition of TGF-β1/Smad3 Pathway in Myocardial Infarction Mice., Cell Physiol Biochem 2016;39:1521-1536, https://www.karger.com/Article/FullText/447855 (1)

  2. Chase Purdy, The human tongue has a sixth sense and its a taste bud that loves carbs. Quartz, qz.com, Sept. 8, 2016, https://qz.com/776857/the-human-tongue-has-a-sixth-sense-and-its-a-taste-bud-that-loves-carbs/ (2)
  3. Wang Y, Ma S, Wang Q, Hu W, Wang D, Li X, Su T, Qin X, Zhang X, Ma K, Chen J, Xiong L, Cao F: Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart. Sci China Life sci 2014;57:201-208. https://www.ncbi.nlm.nih.gov/pubmed/24430557 (3)
  4. Claude Prigent, Editor, Protein Phosphorylation, Publisher: InTech, Chapters published November 29, 2017 under CC BY 3.0 license InTechOpen.com, https://www.intechopen.com/books/protein-phosphorylation (4)
  5. Wenyan Sun, Chunhong Yan, Bess Frost, Xin Wang, Chen Hou, Mengqi Zeng, Hongli Gao, Yuming Kang,and Jiankang Liu,

    Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats., Sci Rep. 2016; 6: 34246.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054377/ (5)

  6. Anupam Bishayee, Deepak Bhatia, Roslin J. Thoppil, Altaf S. Darvesh, Eviatar Nevo, and Ephraim P. Lansky.,  Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms., Carcinogenesis. 2011 Jun; 32(6): 888–896. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314278/ (6)
  7. Holy Bible, Revised Standard Version, Containing the Ole and New Testaments, Thomas Nelson & Sons, New York, 1952, 1 Samuel 14.2, page 297, Haggai 2.19, page 984 https://www.amazon.com/1952-Revised-Standard-Version-Bible/dp/B000U2L3E0 (7)
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Oxidative Stress and Aging; trace minerals and antioxidants

For a more detailed review of the current understanding of how oxidative stress and inflammation are involved in the aging process see this chapter from a longer book: Oxidative Stress and the Aging Brain: From Theory to Prevention, [1]

Mitochondria are the main energy producers in cells. They are involved in breaking down each molecule of glucose (one half of the larger molecule that is commonly known as sugar). During the process of breaking the chemical bonds found in the glucose molecule the free radicals that can cause oxidative damage are produced. When adequate antioxidants are available the free radicals are stabilized before they can cause damage. The body’s internally produced antioxidant enzymes also require the trace minerals copper, zinc and manganese. /Separate topic: An imbalance in copper and zinc can cause health problems./

“Free radicals are chemical species with a single unpaired electron. The unpaired electron is highly reactive as it seeks to pair with another free electron; this results in the production of another free radical. The newly produced free radical is unstable in most cases and, as a result, it can also react with another molecule to produce yet another free radical. Thus, a chain reaction of free radicals can occur, leading to more and more damaging reactions.” [1]

“Several antioxidant defense mechanisms have evolved to protect cell components from the attack of oxidative stress and associated oxidative damage. These mechanisms include antioxidant enzymes, such as SOD, superoxide reductases, catalase, glutathione peroxidases (Gpx), and many heat-shock proteins.” “SOD exists in two forms: Cu/ZnSOD is present primarily in the cytoplasm while MnSOD is present primarily in the mitochondria.” [1]

More information about manganese superoxide dismutase (MnSOD) and how mitochondria function is available here: MnSOD in Oxidative Stress Response-Potential Regulation viaMitochondrial Protein Influx [2]

Supplementing the diet with a manganese and other trace minerals may be helpful as manganese and other trace minerals may be chelated by glyphosate, the active ingredient of the herbicide RoundUp. Chelation is a chemical term for the tendency for one chemical to bind with another – take hold and make the other one less freely available in the environment. The process can be helpful in some situations as it can act as a carrier, a taxi cab so to speak, but at other times it is simply removing the other chemical from being available for other uses.

Plant scientists are aware of the problem and there are agricultural suggestions for reducing the negative effects of manganese chelation by glyphosate in the following article: What About Glyphosate-Induced Manganese Deficiency? The effects of glyphosate’s chelation of iron, copper and zinc is also included in addition to the discussion of manganese. [3] The summary of plant yield research found that improved crop yields were produced when manganese, copper and zinc were applied as a supplemental fertilizer a certain amount of time after the glyphosate containing herbicide was applied to the fields:

“The greatest soybean yield response on high organic soils
was with both Mn and Cu applied 8 to 12 days after the glyphosate.
The highest yields for corn were obtained by foliar-applying Zn 15
days after glyphosate was applied in northwestern Indiana,” [3]

So if plant health scientists recommend supplementing with manganese, copper and zinc for best plant health do human health scientists? Some do, but the topic is still considered alternative medicine rather than being a mainstream medical recommendation. [4] Risks of increased toxicity from trace metals that have negative health effects such as aluminum. [4]

Antioxidant rich foods or supplements that were discussed in the chapter on Oxidative Stress and Aging include vitamin E, which had positive results when used as a supplement in animal studies and mixed results in studies with humans, addition of whole foods such as nuts which are a good source of vitamin E and other nutrients had more consistent positive results in human clinical research studies; Green Tea and its active metabolite EGCG; blueberries, spinach and spirulina, a blue-green algae. [1]

  • 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.
  1. Carmelina Gemma, Jennifer Vila, Adam Bachstetter, and Paula C. Bickford, Chapter 15: Oxidative Stress and the Aging Brain: From Theory to Prevention, from Brain Aging: Models, Methods, and Mechanisms. Riddle DR, editor. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. https://www.ncbi.nlm.nih.gov/books/NBK3869/
  2. Demet Candas and Jian Jian Li, MnSOD in Oxidative Stress Response-Potential Regulation viaMitochondrial Protein Influx, Antioxid Redox Signal. 2014 Apr 1; 20(10): 1599–1617. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942709/
  3. Don M. Huber, What About Glyphosate-Induced Manganese Deficiency?, Fluid Journal, Fall 2007, http://www.agweb.com/assets/import/files/58p20-22.pdf
  4. Anthony Samsel and Stephanie Seneff, Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies, Surg Neurol Int. 2015; 6: 45. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392553/
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Good news: Baths can be less exhausting than showers

Yes, autoimmune disease can be exhausting and it can be confusing for other people to understand because autoimmune disease may not have obvious symptoms. A person with an autoimmune disorder may suffer from severe pain or other symptoms throughout their body but not have lab tests that show obvious problems to a physician. Autoimmune antibodies are known for a few types of disorders and those can be screened for if the lab test is ordered but not all autoimmune antigens have been identified.

Magnesium deficiency may be an underlying issue though for many/most autoimmune disorders, so taking an Epsom salt bath can provide improved magnesium absorption through the skin and allow a person to sit down to wash their hair and shave their legs (if desired). No promises though, that a nap might not still be desired after the exertion of bathing while sitting, or before the exertion of blow-drying long hair.

Fibromyalgia and chronic pain problems may have autoimmune origins [3] and/or may have to do with our cell’s energy workhouses, the mitochondria, running out of their preferred energy source — magnesium. They use calcium but it can overwork them to the point of cell death. In normal physiology membrane transport systems, also called ion channels, carefully control how much calcium is allowed into the interior of mitochondria. Something called ruthenium-red (RuRed)* and magnesium ions are involved in controlling the entry of calcium ions through the transport channels. [1, 2]

A deficiency of magnesium may allow excess calcium to enter the mitochondria and cause overexcitation and even lead to death of the mitochondria.

Mitochondria are actually similar to bacteria and have their own DNA that in nature always matches the mother’s mitochondria’s DNA but that is a different story.

*(RuRed) – not a nutrient I didn’t know about – it’s a dye used in labs that selectively binds with some things but not others so it is used for identification purposes with unknown samples — roughly.

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.

  1. http://ajpcell.physiology.org/content/287/4/C817
  2. https://www.researchgate.net/publication/20680823_Ruthenium_red_and_magnesium_ion_partially_inhibit_silver_ion-induced_release_of_calcium_from_sarcoplasmic_reticulum_of_frog_skeletal_muscles
  3. https://www.ncbi.nlm.nih.gov/pubmed/24435355