The liver and fat soluble vitamins
The live and fat soluble vitamins

LIVER FUNCTION AND HAIR HEALTH

The liver is a vital organ that detoxifies various molecules, synthesis proteins and produces substances necessary for digestion, growth and immune competence.  Other role include regulation of blood glucose, breaking down red blood cells and producing various hormones.

The liver produces bile which aids the breakdown of fat and also converts thyroxine (thyroid hormone) to its more active form for increased metabolism.  The liver is made up of highly specialised tissue mainly made up of liver cells called hepatocytes.  Hepatocytes are able to perform a number of biochemical activities at a high capacity, most of these activities are essential to maintain essential biological functions.

Whilst there are no specific types of hair loss directly linked to poor liver health a number of biological processes regulated by the liver such as immune competence, and growth factor and hormone production contribute to the severity of hair loss conditions such as alopecia areata, androgenic alopecia and telogen effluvium.

Liver function in relation to hair loss

Functions of the liver.

THE LIVER AND METABOLIC FUNCTIONS

Metabolism is a complex chemical process that involves the building up and breaking down of products to create energy and sustain life.  The building of a product from smaller components is called anabolism and the breaking down of components is called catabolism. In the body, there is a constant cycle of anabolism and catabolism to maintain body systems.  when we eat food it is broken down for absorption and then assembled for storage or transported for immediate use.

One essential metabolic process the liver carries out is the breakdown of excess protein consumed in the diet.  These excess proteins are not required and contain a potentially toxic amino group.  In the blood this amino group is removed to form a ketoacid and ammonia.

Ammonia is then converted to urea by a process known as the Krebs-Henseleit cycle or cleared by incorporation into the amino acid glutamine.  The Krebs-Heneleit cycle allows carbon dioxide to be reacted with ammonia and then excreted by the kidneys in the urine.  Every cycle requires 2 ATP molecules, ATP is the energy currency of the body.

The liver is also responsible for the breaking down of hormones such as insulin and oestrogen, transforming them into inactive products for removal from the body in bile.  Hormones are released by endocrine glands such as the thyroid, the pancreas, and ovaries.

If there is an excess of a particular type of hormone the liver will remove the excess until the hormone level exceeds the capacity of the livers elimination capabilities.  In this way, a normally functioning liver can maintain normal hormone function when endocrine function is disturbed.

Hormones such as insulin and estrogen are beneficial to hair growth but in the long term interrupt the normal mechanisms that support keratin synthesis.  Hormone imbalance through slow clearance can lead to a number of non-specific symptoms including hair loss.

The formation of urea in the body

The formation of urea.

THE LIVER PRODUCES CATALASE FOR THE REDUCTION OF HYDROGEN PEROXIDE

Hydrogen peroxide is the simplest peroxide and the most reactive oxygen species.  In humans it is a product of metabolic processes and toxic to cells.  Hydrogen peroxide causes damage to proteins, DNA and cell membrane lipids.  Catalase, a heme dependant  enzyme produced mainly by the liver, is able to convert hydrogen peroxide into oxygen and water.  The activity of catalase is dependent on the presence of heme, it has the highest turnover of all enzymes in the body.

Catalase inhibition by impaired production of the liver or the absence of heme, contributes to the premature greying of hair.  When catalase levels or activity declines, hydrogen peroxide interferes with the production of melanin and hair grows without it’s usual pigment and appears grey or white in colour.

When catalase is insufficient, hydrogen peroxide is broken down by glutathione instead.  Glutathione production is dependant on cysteine and increased glutathione need leaves less available sulphur containing amino acids are available for keratin synthesis in the hair fibre.

Heme is a precursor to hemoglobin also synthesised by the liver.  Adequate heme synthesis is dependent on adequate iron levels the body, an iron deficiency will limit heme availability and reduce catalase activity.

Catalase deficiency and grey hair

Catalase deficiency leads to premature greying of hair.

THE LIVER REGULATES BLOOD GLUCOSE AND CARBOHYDRATE METABOLISM

Glucose levels are an important fuel source for normal keratin cell metabolism.  Keratin cells use glucose along with amino  acids and fats for the energy required to survive and grow.  Red blood cells, that deliver oxygen to the hair follicle are entirely dependant on glucose.

The liver plays a central role in maintaining blood glucose levels.  When food is consumed, and glucose excess can be stored in the liver as glycogen.  When glucose levels are low this glycogen can be degraded to release glucose.  When glycogen stores are depleted, cortisol and glucagon stimulate the conversion of amino acids into glucose for circulation in the blood stream.  Cortisol also stimulates the breakdown of collagen that is found in the extracellular matrix that house the hair follicle.  This leads to a shallow hair fibre shaft the limits the differential potential of keratin cells and less anchorage of the hair follicle. Eventually the continual breakdown of collagen will lead to a short term condition known as telogen effluvium, if this condition is not corrected then the hair loss will be prolonged as new hair will not grow back in its place leading to diffuse hair loss.

Whilst glucose levels are important for hair growth, high and low levels of blood glucose slow down calcium-dependant differentiation and of keratin cells leading to a thinner hair fibre with a shorter growth cycle.

Low blood sugar levels lead to high levels of cortisol as the body seeks to increase blood sugar levels by converting amino acids into proteins.  This biological process in the short term is beneficial and fills a requirement for glucose, in the long term this can lead to the loss of lean body mass due to the continual breakdown of muscle for the provision of glucose.  If the liver is slow in the process of converting amino acids and fats into glucose cortisol levels will remain high and blood sugar will remain insufficient.

When blood glucose concentrations are high, the effects of the keratin cell insulin receptor and insulin-like growth factor 1 are inhibited leading to reduced keratin cell proliferation.

Androgenic alopecia has been linked to impaired glucose utilisation of hair keratin cells.  High levels of glucose are known to affect the actions of insulin by regulating genes that control the uptake of glucose by insulin-like growth factor 1 and insulin.  This control prevents glucose entering the cell creating a cycle where high glucose levels means that less glucose enters keratin cells leaving these cells unable to take up their essential fuel source.

Functions of the liver blood glucose

The liver maintains blood glucose levels to regulate normal hair growth.

LIPIDS AND STEROID HORMONES ARE REGULATED BY THE LIVER

Lipid (fat) metabolism involves the breaking down and building of lipids in cells.  Lipids can be stored for energy, or used as structural and functional units like those involved in the construction of cell membranes.  Lipids are provided by the diet or synthesised by the liver, most lipids obtained by the diet are found in the body as triglycerides or cholesterol.   Other lipids found in the body are membrane lipids and fatty acids.

Lipids to not mix with water and need to be made water-soluble before the can be absorbed through the intestinal walls.  Digestion of lipids start with lipase but a majority of the work is performed by bile salts from the liver and pancreatic lipase.

Lipids are broken down into triglycerides and cholesterol and require special proteins to transported in the blood, these are known as lipoproteins. Lipoproteins are classified by density and control the sub-type of lipid they can transfer.

Very-low-density proteins carry triglycerides synthesised by the body, low-density proteins carry cholesterol to peripheral tissues and high-density lipoproteins carry cholesterol back to the liver for removal.

Cholesterols are essential to normal biological function as they can be modified to form different steroid hormones such as progesterone and testosterone.  Over 70% of cholesterol synthesis is carried out in the liver.

Other lipids that are important for normal cellular growth and metabolism include:

Steroids – important signalling molecules

Ketone bodies – produce energy

and Glycolipids – maintain the lipid bilayer of the cell membrane

THE LIVER SUPPORTS STORAGE OF FAT SOLUBLE VITAMINS

The liver controls the uptake and storage of fat-soluble vitamins.  The bile secreted by the liver is necessary for the emulsification of fats so they can be absorbed in the intestines.  Impaired bile output will impede the uptake of vitamin A, D, E and K.

Vitamin A  (Retinol) – Essential for immune function and cell-cell communication.  Levels of vitamin A in the body can be measures by assessing blood retinol levels,  but the measurement of vitamin A status is limited as levels do not drop until liver stores are depleted.  Vitamin A metabolism is altered in scarring alopecia (cicatrices alopecia) [1] and it has been determined that a vitamin A levels contribute to severity of scarring.  Low dose vitamin A supplementation combined with cysteine supplementation reduces shedding in cases of telogen effluvium [2] and increased retinol binding expression protein in alopecia areata supports the evidence that vitamin A plays a role in hair loss [3].

Vitamin D

Vitamin D is required for the uptake of calcium in the intestines,.  Calcium is an important mediator of the differentiation of keratin cells into mature, robust adequately filamented keratin cells..  Research shows that a low levels of vitamin D are linked to androgenic alopecia and alopecia areata [4].  Low zinc has been reported to be a contributing factor to vitamin D deficiency, when zinc is low vitamin D receptor is unregulated in the liver, hair follicle and other cells in the body.  The increase in vitamin D receptor increases demand due to the similar roles zinc and vitamin D play in the role of maintaining immune function.  Supplementing with zinc is preferable to supplementing with vitamin D for hair regrowth as this will lower the biological demand for vitamin D.  Increasing zinc levels will aid keratin cell synthesis and liver uptake of vitamin D.

Vitamin E

A small trial from 2010 found that vitamin E supplements improved hair growth in people with hair loss. It’s thought that the vitamin’s antioxidant properties helped reduce oxidative stress in the scalp.  Vitamin E is secreted by the sedbabcous glands

Vitamin K 

Vitamin K helps to regulate calcium deposition in the body; because of this, it helps prevent blood vessel calcification (as seen in female pattern hair loss).

THE LIVER DETOXIFICATION PATHWAY

The liver removes toxins and metabolic waste by converting them to water-soluble compounds with sulphur so that can be excreted in the urine.  Substances that are not water-soluble are excreted in the bile, the bile is transported into the intestines and excreted into the faeces.

Phase I detoxification prepares substances for phase-two detoxification.  Key nutritional requirements for phase one detoxification include vitamins: A, E, and B3.  Minerals required include zinc and magnesium. Essential fatty acids are also required for phase one.

Phase II detoxification transforms any toxic agents, so they can be excreted in the urine or in the faeces. If phase-two processing fails to keep up with phase-one, free radicals can accumulate in the form of reactive intermediates.   A reactive intermediate is a short-lived, high-energy, highly reactive molecule, when your liver fails to process these intermediates efficiently they begin to build up.  If the liver cannot process intermediates much like a factory line production, liver function will slow down considerably [1-3].

5 SIGNS YOUR LIVER IS BEING OVERWORKED

  1. You find it difficult to lose weight; the liver is the primary metaboliser of fat in the body.  When liver function is below normal, it eventually impacts your ability to burn fat.  In addition to weight gain, it makes losing any extra pounds nearly impossible.
  2. You have trouble digesting fatty foods; If you find that you have a fatty or distended stomach after eating fatty foods, your liver may be functioning poorly.  Bile is required to digest and absorb fat, if you are not digesting fats efficiently, then you are not absorbing adequate amounts of the fat-soluble vitamins A, D, E, and K- vital for healthy hair, immunity, bones, and much more.
  3. You have dry, slow growing hair; the liver is the main metabolic site of the body.  It produces enough energy to sustain thousands of necessary functions performed every second by the body’s cells.  Your hair follicles are dependent on a constant supply of energy to grow and regenerate.
  4. You get ill often; the liver is responsible for fighting off infections, and when the liver is overworked, the immune system cannot handle the extra load: leaving you more prone to picking up bugs and infections.
  5. You suffer from bad PMS; the liver regulates our hormone levels, an overworked liver results in elevated levels of estrogen which can lead to mood swings and irritability.

THE FINAL WORD

The liver has an amazing capacity to regenerate itself.  Through diet, nutritional supplementation, and exercise, most types of liver disfunction can be resolved.

  1. Reduce caffeine intake; Caffeine speeds up Phase I detoxification and can increase the burden on an already sluggish liver.
  2. Cut back on alcohol; Alcohol increases Phase I detoxification. A pattern of drinking that brings blood alcohol concentration to 0.08 g /dL on more than 5 days in a month, will affect the liver’s capacity to regulate blood sugar and metabolise fats.  A blood alcohol concentration of 0.08 g/dL will typically occur after 4 alcoholic drinks.
  3. Supplement to support the liver; the liver requires an adequate supply of iron to fully support its detoxification and metabolic processes.  Adequate iron levels are essential for intracellular energy output, from which adenosine triphosphate (ATP) is produced.  Zinc and B complex vitamins are also important for liver health.
  4. Get checked out; If you think you may have digestive or metabolic issues do to liver function see a doctor.  Whilst liver function may appear normal look out for iron deficiencies or low haemoglobin that can impact liver function.

REFERENCES

  1. Everts, H.B., Silva, K.A., Montgomery, S., Suo, L., Menser, M., Valet, A.S., King, L.E., Ong, D.E. and Sundberg, J.P., 2013. Retinoid metabolism is altered in human and mouse cicatricial alopecia. Journal of Investigative Dermatology, 133(2), pp.325-333.Eshraghian A, Hamidian Jahromi A. Non-alcoholic fatty liver disease and thyroid dysfunction: a systematic review. World J Gastroenterol.2014
  2. Hertel, H., Gollnick, H., Matthies, C., Baumann, I. and Orfanos, C.E., 1989. Low dosage retinol and L-cystine combination improve alopecia of the diffuse type following long-term oral administration. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete, 40(8), pp.490-495.
  3. Elmaadawy, E., Elgarhy, L.H. and Shareef, M., 2019. Cellular retinol‐binding protein‐1 expression increases with increasing clinical severity of alopecia areata. Journal of cosmetic dermatology, 18(2), pp.659-664.
  4. Aksu Cerman, A., Sarikaya Solak, S. and Kivanc Altunay, I., 2014. Vitamin D deficiency in alopecia areata. British Journal of Dermatology, 170(6), pp.1299-1304.
  5. Hodges RE, Minich DM. Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. J Nutr Metab. 2015;2015:760689. doi:10.1155/2015/760689
  6. J Hum Nutr Diet. 2015 Dec;28(6):675-86. doi: 10.1111/jhn.12286. Epub 2014 Dec 18.

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